Older Sibling Research Articles

Eye Movements and Behavioural Responses to Gaze-Contingent Expressive Faces in Typically Developing Infants and Infant Siblings.

Studies with infant siblings of children with Autism Spectrum Disorder have attempted to identify early markers for the disorder and suggest that autistic symptoms emerge between 12 and 24 months of age. Yet, a reliable first-year marker remains elusive. We propose that in order to establish first-year manifestations of this inherently social disorder, we need to develop research methods that are sufficiently socially demanding and realistically interactive. Building on Keemink et al. [2019, Developmental Psychology, 55, 1362-1371], we employed a gaze-contingent eye-tracking paradigm in which infants could interact with face stimuli. Infants could elicit emotional expressions (happiness, sadness, surprise, fear, disgust, anger) from on-screen faces by engaging in eye contact. We collected eye-tracking data and video-recorded behavioural response data from 122 (64 male, 58 female) typically developing infants and 31 infant siblings (17 male, 14 female) aged 6-, 9- and 12-months old. All infants demonstrated a significant Expression by AOI interaction (F(10, 1470)=10.003, P < 0.001, ŋp2 =0.064). Infants' eye movements were "expression-specific" with infants distributing their fixations to AOIs differently per expression. Whereas eye movements provide no evidence of deviancies, behavioural response data show significant aberrancies in reciprocity for infant siblings. Infant siblings show reduced social responsiveness at the group level (F(1, 147)=4.10, P=0.042, ŋp2 =0.028) and individual level (Fischer's Exact, P=0.032). We conclude that the gaze-contingency paradigm provides a realistically interactive experience capable of detecting deviancies in social responsiveness early, and we discuss our results in relation to subsequent infant sibling development. LAY SUMMARY: We investigated how infant siblings of children with autism spectrum disorder respond to interactive faces presented on a computer screen. Our study demonstrates that infant siblings are less responsive when interacting with faces on a computer screen (e.g., they smile and imitate less) in comparison to infants without an older sibling with autism. Reduced responsiveness within social interaction could potentially have implications for how parents and carers interact with these infants. Autism Res 2021, 14: 973-983. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Younger HLA-Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplantation (allo-HCT) for Myelodysplastic Syndromes (MDS) Is Associated with Superior Disease-Free Survival Compared to Older HLA-Identical Sibling Donors: CIBMTR Analysis

Background: When older MDS patients present for allo-HCT, HLA-identical sibling donors who are eligible to donate are usually the preferred choice. The age of the HLA-identical sibling donor is likely to be advanced as well. However, the choice between an older HLA-identical sibling donor and younger HLA-matched unrelated donor remains unclear. Methods: Using the center for international blood and marrow transplant research (CIBMTR) database, we identified adults aged ≥50 years with MDS who underwent allo-HCT from older HLA-identical sibling donor (age ≥50) or younger 8/8 (HLA-A, -B, -C and -DRB1) well matched unrelated donor (MUD) (age ≤ 35) between the years 2011-2017. In prior studies, compared to older MUD, allo-HCT from MUD younger than age 35 was associated with superior outcomes (Shaw BE et al. BBMT 2018, Kollman C et al. Blood 2016, CIBMTR internal data). Hence, in the current analysis, the MUD arm was restricted to those aged ≤35. Key exclusion criteria were allo-HCT from mismatched unrelated donor, haploidentical donor, cord blood donor and ex-vivo T-cell depleted grafts. Overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM), relapse, acute and chronic graft versus host disease (GVHD) were evaluated. Survival analysis was done using Kaplan-Meier method and significant predictors were evaluated using Cox-proportional hazard regression method. Multivariate regression model included main effect (donor age group) and covariates (patient age, gender match, CMV match, disease subtype, R-IPSS at HCT, comorbidities score (HCT-CI), Karnofsky performance status, prior therapy, interval between diagnosis and transplant, conditioning intensity, stem cell source, GVHD prophylaxis, ATG/campath use, transplant year, and center affect). Fine and Gray (F-G) model for competing risks was used for analysis of NRM and relapse. Results: Of 1761 patients who met the study criteria, 646 patients received allo-HCT from older HLA-identical sibling and 1115 patients from younger MUD. Cohorts were similar for age, sex, Karnofsky performance status, HCT-CI, R-IPSS at HCT, time from diagnosis to transplant, prior therapy, graft type and conditioning intensity. Notable differences between donor groups included donor age (HLA identical sibling donor- median age 61.3 years vs. MUD- median age 25.2 years) and use of ATG/campath (HLA identical sibling donor 14% vs MUD 37%). In multivariable analysis, there was a significant difference in DFS (p=0.01) but not OS (p=0.14) among donor groups. Compared to MUD ≤35 years, DFS was inferior in HLA identical sibling donor age ≥60 but not in HLA-identical sibling donor age 50-59 (Table 1) (Figure 1A). In multivariate analysis using Fine and Gray model, the risk of relapse was significantly higher in patients receiving allo-HCT from HLA-identical sibling donor compared to MUD≤35 (Table 1, figure 1B). There was no significant difference in NRM between HLA-identical sibling donors and MUD ≤35 (overall p=0.07, table 1). HLA-identical sibling donor cohort was associated with lower risk of acute GVHD (p&amp;lt;0.001) and chronic GVHD (overall p=0.007) as compared to MUD ≤35 cohort (table 1). Results were consistent across all subgroups. Conclusions: Our results demonstrate a superior DFS that is mediated by superior disease control for MDS patients undergoing allo-HCT from younger MUD compared to older HLA-identical sibling donors. Our results should inform donor selection algorithms for older MDS patients undergoing allo-HCT. Disclosures Nakamura: Alexion: Other: Support on a meeting presentation; Kadmon Corporation: Other: Advisory board meeting; Kyowa-Kirin: Other: Support on a meeting presentation; Merck: Other: advisory board meeting; Magenta Therapeutics: Other: Advisory board meeting; Viracor: Consultancy; Celgene: Other: Support on seminar; NapaJen Pharma: Consultancy. Oran:Celgene: Consultancy; ASTEX: Research Funding; Arog Pharmaceuticals: Research Funding. Scott:BMS, Novartis: Research Funding; Alexion, Incyte, Novartis, Regeneron: Consultancy; Agios, BMS: Honoraria.

Effect of sibship asthma on newborns with transient tachypnea of the newborn (TTN)

A number of studies have demonstrated that transient tachypnea of the newborn (TTN) is a risk factor for later asthma. The present study attempts to determine whether older sibling asthma is a risk factor for TTN. Medical records of 1318 newborns from neonatal intensive care and delivery units were studied. None of the subjects were first-born, and thus, all had older siblings. Clinical data of mothers and their children were obtained from medical records. Data items included date of birth, gestational age (GA) at birth, birth weight, gender, mode of delivery including Normal Spontaneous Delivery or caesarean section (CS) and whether pre-labour CS or not, reasons for CS, number of pregnancies, number of children, asthma of mothers and siblings, whether the newborn had TTN or not. Logistic regression analysis was used to assess the association between siblings' asthma and TTN. Pre-labour CS, maternal asthma, GA, babies with large and small birth weight for GA, number of pregnancies and children (three and more) were found to be significantly associated with TTN. Siblings' asthma was found to be independently associated with a diagnosis of TTN. Both pre-labour CS and mothers with asthma were common risk factors for the development of TTN. An association was present between TTN and siblings' asthma even in infants whose mothers did not have asthma.

Using age difference and sex similarity to detect evidence of sibling influence on criminal offending.

Sibling resemblance in crime may be due to genetic relatedness, shared environment, and/or the interpersonal influence of siblings on each other. This latter process can be understood as a type of 'peer effect' in that it is based on social learning between individuals occupying the same status in the social system (family). Building on prior research, we hypothesized that sibling pairs that resemble peer relationships the most, i.e., same-sex siblings close in age, exhibit the most sibling resemblance in crime. Drawing on administrative microdata covering Finnish children born in 1985-97, we examined 213 911 sibling pairs, observing the recorded criminality of each sibling between ages 11 and 20. We estimated multivariate regression models controlling for individual and family characteristics, and employed fixed-effects models to analyze the temporal co-occurrence of sibling delinquency. Among younger siblings with a criminal older sibling, the adjusted prevalence estimates of criminal offending decreased from 32 to 25% as the age differences increased from less than 13 months to 25-28 months. The prevalence leveled off at 23% when age difference reached 37-40 months or more. These effects were statistically significant only among same-sex sibling pairs (p < 0.001), with clear evidence of contemporaneous offending among siblings with minimal age difference. Same-sex siblings very close in age stand out as having the highest sibling resemblance in crime. This finding suggests that a meaningful share of sibling similarity in criminal offending is due to a process akin to peer influence, typically flowing from the older to the younger sibling.

Reassessing the Effect of Older Sisters on Sexual Orientation in Men.

This research reanalyzed questionnaire data from 8279 homosexual and 79,519 heterosexual men who participated in 2005 in an internet-based research project sponsored by the British Broadcasting Corporation. It focused on parameters of sibship composition (older brothers, older sisters, younger siblings) previously shown or hypothesized to influence sexual orientation in males. The results included the usual finding that older brothers increase the odds of homosexuality in later-born males. As predicted, older sisters also increase those odds, although by a lesser amount than older brothers. Other results confirmed that the odds of homosexuality are increased in only-children, the amount of increase being equal to that produced by one older brother and greater than that produced by one older sister. Finally, the results indicated that younger siblings have no effect on the odds of homosexuality in males. These results might be explained by the hypothesis that two different types of immune responses in pregnant women can affect the future sexual orientation of their male fetuses. One type of response affects fetuses in first pregnancies and reduces subsequent fertility. The other type affects fetuses in later pregnancies and has little or no effect on fertility. Finally, we conducted an estimate of combined sibship effects. Men who were exposed to any of the influences that we identified (being an only-child or having an older sibling) had 27% greater odds of homosexuality than did subjects who were exposed to none of these influences (i.e., the first-born of two or more children).

Incidence of childhood burn injuries and modifiable household risk factors in rural Ghana: A cluster-randomized, population-based, household survey

BackgroundWe aimed to determine the incidence of childhood burn injuries in rural Ghana and describe modifiable household risk factors to inform prevention initiatives. MethodsWe performed a cluster-randomized, population-based survey of caregivers of children in a rural district in Ghana, representing 2713 households and 14,032 children. Caregivers were interviewed regarding childhood burn injuries within the past 6 months and household risk factors. Results357 households were sampled. Most used an open fire with biomass fuel for cooking (85.8%). Households rarely cooked in a separate kitchen (10%). Stove height was commonly within reach of children under five years (<1 m; 96.0%). The weighted annualized incidence of CBI was 63 per 1000 child-years (6.4% of children per year); reported mean age was 4.4 years (SD 4.0). The most common etiology was flame burn. Older age (OR 0.89, 95% CI 0.8–1.0) and households with an older sibling ≥12 years (OR 0.58, 95% CI 0.3–1.3) seemed to be associated with lower odds of CBI. ConclusionsChildhood burn injury is common in rural Ghana. Opportunities exist to reduce the risk of childhood burn injury childhood burns in rural settings by supporting the transition to safer cooking arrangements, child barrier apparatuses in homes without older children, and/or development of formal childcare programs.

Adapting the Six-Part Storymaking Method for use with siblings of infants on the neonatal intensive care unit

When an infant is hospitalized on the neonatal intensive care unit (NICU) it can have a profound influence on the psychosocial well-being of the infant and their older sibling(s). This article presents a case vignette of the use of the Six-Part Storymaking Method with the sibling of an infant hospitalized on the NICU. The article reviews the therapeutic aims and benefits of the intervention, including: supporting emotional expression, providing opportunity for the sibling to be deeply witnessed by caregivers, therapist and hospital staff, empowering the sibling to inhabit the big sibling role and fostering insight into the sibling’s thoughts, feelings and behaviours as related to their infant’s hospitalization. Considerations for facilitation and assessment are also discussed.

Associations between prenatal phthalate exposure and sex-typed play behavior in preschool age boys and girls

Phthalates, a class of chemicals found widely in consumer products including plastic toys, food contaminants and food packaging, personal care products, cosmetics, air fresheners, and some medications, have been shown to be anti-androgenic in numerous laboratory and epidemiological studies. In a prior cohort enrolled in 2000–2002, we observed associations between prenatal urinary concentrations of di-ethyl hexyl phthalate (DEHP) and dibutyl phthalate (DBP) metabolites and less male-typed play behavior in preschool age boys. The aim of this study was to examine phthalate exposure in pregnancy in relation to play behavior at age 4 years in a larger cohort of pregnant women enrolled in The Infant Development and the Environment Study (TIDES) between 2010 and 2012 at four study sites (Minneapolis, MN; Rochester, NY; San Francisco, CA; Seattle, WA). Maternal urinary metabolites of DEHP, DiBP, DnBP, BBzP, and DEP were measured during the first (n=498) and third trimester (n=468) and mothers completed the Preschool Activities Inventory (PSAI), a validated maternal questionnaire designed to assess child toy preference and sex-typed play behavior when children were 4–5 years of age. After adjusting for child age, maternal education, race, urine dilution, parental attitudes about opposite sex-typed play behavior, and presence of a same sex older sibling, we observed associations between first trimester (mean 10.7±2.1 weeks gestation) (log10) SpG-adjusted MnBP, MiBP, and MBzP and lower masculine scores in boys (β-coefficient [95% confidence intervals]: MnBP −2.18, [-4.16, −0.20]), MiBP −2.1[-4.3,0.1], and MBzP -2.42 [-4.12, −0.71]). In girls, first trimester maternal urinary MBzP was associated with lower masculine scores (-2.12 [-3.98,-0.25]), while third trimester (mean 32.8±3.0 weeks gestation) maternal urinary MiBP was associated with higher masculine scores (2.69 [0.68,4.70]). Third trimester maternal urinary phthalate levels were not associated with play behavior in boys. These findings in boys are largely consistent with previous studies that report that prenatal phthalate exposure is associated with less masculine play behavior. No associations in girls have been previously reported.

Where You Lead, I Will Follow: Exploring Sibling Similarity in Brain and Behavior During Risky Decision Making.

This exploratory study examined whether social learning increases similarity in adolescent siblings’ behavior and neural patterns during risky decision making. Participants included 86 adolescents (43 sibling dyads; younger siblings: M age = 12.2 years; 22 females; older siblings: M age = 14.6 years; 20 females) who completed questionnaires, and a decision‐making task during an fMRI scan. Younger siblings became more similar to their older siblings’ risky decision making after observing their older sibling take risks). Younger siblings who reported greater modeling of their older sibling, and less differentiation from them, showed increased neural similarity to their older siblings in the ventromedial prefrontal cortex, and the right anterior insula and ventral striatum, respectively. These findings highlight siblings as salient social agents in how adolescents process risky decision making.

A gendered typology of tobacco use among college students

Abstract Background Smoking habits initiated during the adolescent period often persist into adulthood leading to tobacco and nicotine dependence with associated morbidity and premature mortality. Parental smoking has been associated with early tobacco dependence on their children. An understanding of students' smoking patterns in relationship to parents' smoking habits is crucial to informing the establishing of a smoking reduction intervention in students. Methods Latent Class Analysis (LCA) was used to characterize the different patterns of smoking among 361 Irish university students. The participants were enrolled in this cross-sectional study by inviting them to complete an online survey. Results Three groups were identified: (1) Chain smokers (n = 92, 25.52%). (2) Moderate tobacco users (n = 124, 34.60%). (3) Experimenters (n = 145, 40.16%). The predominantly male 'chain-smokers' groups (class 1) has a higher probability of using tobacco several times a day, have both parents as tobacco users and both parents smoking in the home compared to the 'moderate tobacco users' group (class 2) and 'experimenters' groups (class 3) which are both predominantly females. The majority (70.40%) of the chain smokers source their tobacco from family members (either parents or an older sibling); moderate tobacco users (84.74%), from friends and experimenters (100%) buy themselves. Conclusions This study reveals the predictors of tobacco use patterns among students and can inform smoking reduction intervention and strategies among students. Key messages Regulating tobacco access will checkmate use among teens/young adults. Understanding how parenteral smoking habits and tobacco access influences use and abuse among students is crucial to instituting intervention strategies.

Whole exome sequencing revealed a novel homozygous variant in the DGKE catalytic domain: a case report of familial hemolytic uremic syndrome

BackgroundAtypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia caused by small vessel thrombosis, thrombocytopenia, and renal failure. The common cause of aHUS is a dysregulation in the alternative complement pathway. Mutations in none complement genes such as diacylglycerol kinase epsilon (DGKE) can also result in this syndrome.Case presentationHere, we report on a 19-year-old female with the clinical diagnosis of aHUS, who has unaffected consanguineous parents and an older sibling who was deceased from aHUS when she was seven months old.We performed whole exome sequencing (WES) followed by evaluation of detected variants for functional significance, using several online prediction tools. Next, in order to confirm the detected pathogenic variant in proband and segregation analysis in her family, Sanger sequencing was done. The novel variant was analyzed in terms of its impact on the protein 3-dimensional structure by computational structural modeling.The results revealed that the proband carried a novel homozygous missense variant in DGKE located in exon 6 of the gene (NM_003647.3, c.942C > G [p.Asn314Lys]), and in silico analysis anticipated it as damaging. Protein computational study confirmed the influence of potential pathogenic variant on structural stability and protein function.ConclusionWe suggest that some variations in the catalytic domain of DGKE like p.Asn314Lys which can cause alterations in secondary and 3-D structure of protein, might lead to aHUS.

For which younger siblings of children with autism spectrum disorder does parent-mediated intervention work?

In this second of two primary papers, we examined two pre-intervention characteristics that might describe for whom a parent-implemented intervention, "Improving Parents As Communication Teachers," worked. Investigators randomized 97 high-risk siblings and their primary parent to either the Improving Parents As Communication Teachers or control group, used intent-to-treat analysis, and used assessors and coders who were blinded to group assignment. We predicted that a combined risk score (incorporating young siblings' sex, multiplex status, and behavioral risk) would describe the subgroup for whom Improving Parents As Communication Teachers affected the targeted skills related to reducing communication challenges. We also predicted that pre-intervention level of parents' depressive symptoms would describe the parents whose parenting stress and effectiveness as parents would be improved by learning to use Improving Parents As Communication Teachers. In girls with only one older sibling with autism spectrum disorder and who scored at low risk on an autism spectrum disorder screen, parental receipt of Improving Parents As Communication Teachers training had an indirect effect on children's expressive language ability or autism spectrum disorder diagnosis through earlier effects on high-risk siblings' intentional communication or expressive vocabulary. We did not confirm our prediction regarding Improving Parents As Communication Teachers' effect on parenting-related stress or sense of parenting effectiveness.

Sibling Configuration as a Moderator of the Effectiveness of a Theory of Mind Training in Children with Autism: a Randomized Controlled Trial

This RCT investigated whether participants’ sibling configuration moderated the effect of a Theory of Mind (ToM) intervention for children with autism. Children with autism aged 8–13 years (n = 141) were randomized over a waitlist control or treatment condition. Both having more siblings, as well as having an older sibling were related to better outcomes on measures of ToM-related behavior and social cognition, but not ToM knowledge or autistic features in general. The finding that these associations were limited to practical skills addressed in the intervention, seems to indicate that having more siblings and having an older sibling provides enhanced opportunities for children with autism to practice taught skills in the home environment.

"Sibling relationships in older adulthood: Links with loneliness and well-being": Correction.

Reports an error in "Sibling relationships in older adulthood: Links with loneliness and well-being" by Clare M. Stocker, Megan Gilligan, Eric T. Klopack, Katherine J. Conger, Richard P. Lanthier, Tricia K. Neppl, Catherine Walker O'Neal and K. A. S. Wickrama (Journal of Family Psychology, 2020[Mar], Vol 34[2], 175-185). In the original article, the df value is incorrect in the following sentence in the first paragraph of the Predictors of Individual Differences in Older Adults' Sibling Relationships section of the Results: "The global F-statistic for warmth was significant (F = 16.55, df = 3, 632, p < .001)." The correct value is "df = 3, 601." (The following abstract of the original article appeared in record 2019-46911-001). Researchers have documented associations between family relationships and a variety of well-being outcomes. Yet, sibling relationships, the longest lasting relationships in most people's lives, have received very little research attention beyond young adulthood. The goals of the current study were to: provide descriptive information about sibling relationships in later adulthood, investigate predictors of individual differences in sibling relationship quality, and examine associations among sibling relationship quality, loneliness, and well-being in later adulthood. The sample included 608 older adults (329 men, 279 women) who were 64.6 years old (SD = 4.58) on average. Participants provided self-report data about their relationships and well-being. Results showed that older adults reported high levels of sibling warmth and low levels of sibling conflict and parental favoritism. Sister-sister pairs had warmer sibling relationships than other gender-compositions. Sibling conflict and parental favoritism were positively associated with symptoms of depression, anxiety, hostility, and loneliness. Sibling warmth was negatively associated with loneliness. Loneliness partially mediated the associations between sibling relationship quality and well-being. Results from this study highlight the importance of sibling relationships in older adults' health and well-being. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Predictors of Opioid Misuse During Emerging Adulthood: An Examination of Adolescent Individual, Family and Peer Factors

IntroductionOpioid misuse has reached epidemic proportions among emerging adults in the U.S. To inform prevention efforts, this study examined adolescent factors related to alcohol and marijuana (AM) use that are associated with a higher or lower risk for opioid misuse during emerging adulthood. MethodsWe used 11 waves of survey data from a diverse California cohort (N = 6,509). Predictor variables from waves 1-7 (ages 11-17) included individual (resistance self-efficacy, positive expectancies) family (older sibling and important adult use), and peer (perceived norms, time spent with peers who use, peer approval) factors. Opioid misuse at wave 8 (mean age = 18.3) and wave 11 (mean age = 21.6) included heroin and nonmedical prescription drug use. ResultsInitial latent growth models (LGMs) indicated that nearly all intercepts and slopes for individual, family, and peer AM factors predicted opioid misuse at waves 8 and 11. These associations were reduced to non-significance after adjusting for prior other substance use with the exception of three intercepts: positive expectancies, peer approval, and older sibling use predicted a higher probability of opioid misuse at wave 8. ConclusionsStronger AM positive expectancies, perceived peer approval of AM use, and older sibling AM use during adolescence are associated with a higher likelihood of opioid misuse during the transition to emerging adulthood. However, most adolescent factors were no longer associated with subsequent opioid misuse after adjusting for history of other substance use, highlighting the importance of considering the larger context of substance use in studies of opioid misuse among young people.

Using a sibling-adoption design to parse genetic and environmental influences on children's body mass index (BMI).

Dietary and physical activity behaviors formed early in life can increase risk for childhood obesity and have continued negative consequences for lifelong health. Previous research has highlighted the importance of both genetic and environmental (e.g., cultural environment or parental lifestyle) contributions to obesity risk, although these studies typically involve genetically-related individuals residing in the same household, where genetic similarity and rearing environment are inextricably linked. Here we utilize a sibling-adoption design to independently estimate genetic and environmental contributions to obesity risk in childhood and describe how these influences might vary as children age. As part of a prospective adoption study, the current investigation used data from biological siblings reared either apart or together, and nonbiological siblings reared together to estimate the contributions of genetics and environment to body mass indices (BMI) in a large cohort of children (N = 711). We used a variance partitioning model to allocate variation in BMI to that which is due to shared genetics, common environment, or unique environment in this cohort during middle childhood and adolescence. We found 63% of the total variance in BMI could be attributed to heritable factors in middle childhood sibling pairs (age 5–11.99; 95% CI [0.41,0.85]). Additionally, we observed that common environment explained 31% of variation in BMI in this group (95% CI [0.11,0.5]), with unique environment and error explaining the remaining variance. We failed to detect an influence of genetics or common environment in older sibling pairs (12–18) or pairs spanning childhood and adolescence (large sibling age difference), but home type (adoptive versus birth) was an important predictor of BMI in adolescence. The presence of strong common environment effects during childhood suggests that early interventions at the family level in middle childhood could be effective in mitigating obesity risk in later childhood and adolescence.

Handedness and Birth Order Among Heterosexual Men, Gay Men, and Sao Praphet Song in Northern Thailand.

Previous research has examined handedness and birth order to inform sexual orientation and gender identity/role expression development; however, sexual orientation and gender identity/role expression have rarely been disentangled to provide a more nuanced perspective. In Thailand, we investigated sexual orientation and gender identity simultaneously via comparison of 282 heterosexual men, 201 gay men, and 178 sao praphet song-i.e., androphilic, markedly feminine males recognized as a "third" gender. Handedness was examined as: extremely left-handed, moderately left-handed, ambidextrous, moderately right-handed, or extremely right-handed. Birth order was examined as numbers of older and younger brothers and sisters, by using Berglin's, fraternal, and sororal indices, and by examining the older brother odds ratio and sibling sex ratio. Compared with heterosexual men, gay men and sao praphet song were more likely to be extremely right-handed. Sao praphet song were also more likely to be extremely left-handed than heterosexual and gay men. Heterosexual men and sao praphet song had later sororal birth order compared with the expected Thai population value, suggesting stopping rules influenced when probands' mothers ceased having children. These findings provide new insights and replicate previous findings in a non-Western sample. Regarding handedness, in males, mechanisms related to extreme right-handedness likely influence the development of androphilia, whereas mechanisms related to both extreme right- and extreme left-handedness likely explain the combination of androphilia and feminine gender identity/role expression. Regarding birth order, similar to the conclusions of some prior research, stopping rules pose a challenge for testing the fraternal birth order effect.

Identification of a novel WAS mutation in a South African patient presenting with atypical Wiskott-Aldrich syndrome: a case report

BackgroundThe X-linked recessive primary immunodeficiency disease (PIDD) Wiskott-Aldrich syndrome (WAS) is identified by an extreme susceptibility to infections, eczema and thrombocytopenia with microplatelets. The syndrome, the result of mutations in the WAS gene which encodes the Wiskott-Aldrich protein (WASp), has wide clinical phenotype variation, ranging from classical WAS to X-linked thrombocytopaenia and X-linked neutropaenia. In many cases, the diagnosis of WAS in first affected males is delayed, because patients may not present with the classic signs and symptoms, which may intersect with other thrombocytopenia causes.Case presentationHere, we describe a three-year-old HIV negative boy presenting with recurrent infections, skin rashes, features of autoimmunity and atopy. However, platelets were initially reported as normal in numbers and morphology as were baseline immune investigations. An older male sibling had died in infancy from suspected immunodeficiency. Uncertainty of diagnosis and suspected severe PIDD prompted urgent further molecular investigation. Whole exome sequencing identified c. 397 G > A as a novel hemizygous missense mutation located in exon 4 of WAS.ConclusionWith definitive molecular diagnosis, we could target treatment and offer genetic counselling and prenatal diagnostic testing to the family. The identification of novel variants is important to confirm phenotype variations of a syndrome.

P1716MULTI-NATIONAL SURVEY AMONG NEPHROLOGISTS &amp; TRANSPLANT SURGEONS ABOUT THE SUITABILITY &amp; ACCEPTANCE OF MARGINAL LIVE KIDNEY DONORS REGARDING AGE DISCREPANCY

Abstract Background and Aims Living donor kidney transplantation is the best option for patients on dialysis. There are no guidelines or generally accepted consensus about the acceptable kidney donor age and what is the acceptable donor-recipient age discrepancy. Method This is a cross sectional survey of nephrologists and transplant surgeons about acceptable age of living kidney donors. The survey was sent to participants in different countries and through AST and ERA/EDTA. Results 122 respondents from 22 countries answered 4 questions related to donor age. Most respondents (N=86, 70%) would allow an 18-years old man to donate to his older sibling. However, this percentage would fall to (N=69, 57%) if the donor was an 18-years old woman (P=0.02), reflecting the impact of childbearing period as a major criterion in considering kidney donation. On the opposite side, up to 20% of respondents will decline a very young donor regardless of the gender of the donor. The acceptance rate of a very young donor drops to only 37% if the recipient is 75-year-old (versus 70% in case of younger recipient, P = 0.004). In case of old donor( &amp;gt; 65 years old) old to an 18 year old recipient with expected prolonged waiting time for deceased donor, ( N= 80, 65%) will advise to find an alternative donor but will allow the donation if no alternative donor is available. Conclusion The majority of the nephrologists and transplant surgeons will allow a very young donor to donate to a sibling especially if the donor is a male. However up to 20% will decline this donation regardless of the gender of the donor. The transplant community is divided about allowing a very young donor to donate to a very old recipient. However, the majority will accept &amp;gt; 65 years old donor to donate to an 18 years old recipient with expected prolonged waiting time for deceased donor.

Ancient founder mutation in RUBCN: a second unrelated family confirms Salih ataxia (SCAR15)

BackgroundHomozygous frameshift mutation in RUBCN (KIAA0226), known to result in endolysosomal machinery defects, has previously been reported in a single Saudi family with autosomal recessive spinocerebellar ataxia (Salih ataxia, SCAR15, OMIM # 615705). The present report describes the clinical, neurophysiologic, neuroimaging, and genetic findings in a second unrelated Saudi family with two affected children harboring identical homozygous frameshift mutation in the gene. It also explores and documents an ancient founder cerebellar ataxia mutation in the Arabian Peninsula.Case presentationThe present family has two affected males (aged 6.5 and 17 years) with unsteady gait apparent since learning to walk at 2.5 and 3 years, respectively. The younger patient showed gait ataxia and normal reflexes. The older patient had saccadic eye movement, dysarthria, mild upper and lower limb and gait ataxia (on tandem walking), and enhanced reflexes in the lower limbs. Cognitive abilities were mildly impaired in the younger sibling (IQ 67) and borderline in the older patient (IQ 72). Nerve conduction studies were normal in both patients. MRI was normal at 2.5 years in the younger sibling. Brain MRI showed normal cerebellar volume and folia in the older sibling at the age of 6 years, and revealed minimal superior vermian atrophy at the age of 16 years. Autozygome and exome analysis showed both affected have previously reported homoallelic mutation in RUBCN (NM_014687:exon18:c.2624delC:p.A875fs), whereas the parents are carriers. Autozygosity mapping focused on smallest haplotype on chromosome 3 and mutation age analysis revealed the mutation occurred approximately 1550 years ago spanning about 62 generations.ConclusionsOur findings validate the slowly progressive phenotype of Salih ataxia (SCAR15, OMIM # 615705) by an additional family. Haplotype sharing attests to a common founder, an ancient RUBCN mutation in the Arab population.