Female Siblings Research Articles

Sex differences in islet stress responses support female β cell resilience

ObjectivePancreatic β cells play a key role in maintaining glucose homeostasis; dysfunction of this critical cell type causes type 2 diabetes (T2D). Emerging evidence points to sex differences in β cells, but few studies have examined male-female differences in β cell stress responses and resilience across multiple contexts, including diabetes. Here, we address the need for high-quality information on sex differences in β cell and islet gene expression and function using both human and rodent samples. MethodsIn humans, we compared β cell gene expression and insulin secretion in donors with T2D to non-diabetic donors in both males and females. In mice, we generated a well-powered islet RNAseq dataset from 20-week-old male and female siblings with similar insulin sensitivity. Our unbiased gene expression analysis pointed to a sex difference in the endoplasmic reticulum (ER) stress response. Based on this analysis, we hypothesized female islets would be more resilient to ER stress than male islets. To test this, we subjected islets isolated from age-matched male and female mice to thapsigargin treatment and monitored protein synthesis, cell death, and β cell insulin production and secretion. Transcriptomic and proteomic analyses were used to characterize sex differences in islet responses to ER stress. ResultsOur single-cell analysis of human β cells revealed sex-specific changes to gene expression and function in T2D, correlating with more robust insulin secretion in human islets isolated from female donors with T2D compared to male donors with T2D. In mice, RNA sequencing revealed differential enrichment of unfolded protein response pathway-associated genes, where female islets showed higher expression of genes linked with protein synthesis, folding, and processing. This differential expression was physiologically significant, as islets isolated from female mice were more resilient to ER stress induction with thapsigargin. Specifically, female islets showed a greater ability to maintain glucose-stimulated insulin production and secretion during ER stress compared with males. ConclusionsOur data demonstrate sex differences in β cell gene expression in both humans and mice, and that female β cells show a greater ability to maintain glucose-stimulated insulin secretion across multiple physiological and pathological contexts.

A novel case of two siblings harbouring homozygous variant in the NEUROG1 gene with autism as an additional phenotype: a case report

IntroductionNEUROG1 gene is yet to be associated with a set of human phenotypes in the OMIM database. Three cases have previously been diagnosed with cranial dysinnervation due to biallelic variants in the NEUROG1 gene. This is the fourth and a novel report of a sibling pair harboring a homozygous variant in the NEUROG1 gene with autism as an additional phenotype. A brief review of the literature in conjunction with a genotype–phenotype correlation has been described. A potential hypothesis for the presence of the autistic phenotype in the present case has also been elucidated.Case presentationA female aged 6 years and 9 months born to endogamous and phenotypically healthy parents was diagnosed with global developmental delay, autism spectrum disorder, hearing loss, corneal opacity and no eye blinking. Her MRI of the brain revealed mild peritrigonal white matter hyperintensity, and MRI and CT scan of the temporal bones showed abnormal cranial nerves. The proband’s younger sister, aged 4-years, was similarly affected. Whole exome sequencing was performed in the proband, which revealed a novel homozygous, likely pathogenic, truncating frameshift variant, c.228_231dup (p.Thr78ProfsTer122) in exon 1 of the NEUROG1 gene (ENST00000314744.4). Segregation analysis by Sanger sequencing showed the proband and her younger sister to be homozygotes and their parents to be heterozygous carriers.ConclusionThis is the fourth report across the globe with a variant identified in the NEUROG1 gene to be associated with cranial dysinnervation phenotype. An additional phenotype of autism in two female siblings was a novel observation. We provide a hypothetical framework which could explain the pleiotropic effect of a dysfunctional NEUROG1 protein leading to autism and posit it as a candidate for diagnosis of autism spectrum disorder with congenital cranial dysinnervation disorder.

Gender and age effects on dental and palatal arch dimensions among full siblings.

This study was conducted to investigate the dental and palatal arch dimensions of male and female siblings in relation to gender and age, using three-dimensional (3D) digital casts. This study involved 54 subjects (27 pairs) of male-female siblings aged 15 to 45 years. Dental casts were digitized and analyzed for tooth size (TS), arch width (AW), arch length (AL), arch length discrepancy (ALD), and palatal arch dimensions (PAD). The data obtained were subjected to t-tests, and the palatal curvature (PC) was modeled using a fourth-order polynomial. Significant differences (P < 0.05) between the sexes were found in the mesiodistal TS, particularly in all canines, as well as 16, 36, 46, and 41. Maxillary AW and AL were also significantly (P < 0.05) influenced by sexes. Most arch parameters were more prominent in male siblings, and the effect of age on PC differed between the sexes. In addition, the PC of adolescent females was mostly superimposed on adult females relative to males. Among siblings, males were found to have significantly larger dental arch dimensions than females. Furthermore, PC showed some differences between the sexes in both the frontal and sagittal planes.

Abstract P074: Pregnancy and neonatal outcomes among early-onset colorectal cancer survivors: a nationwide case-control study

Abstract Purpose: Early-onset colorectal cancer (CRC diagnosed before age 50) has risen worldwide, with an increasing number of survivors of reproductive age. We aimed to investigate the risk of adverse pregnancy and neonatal outcomes among early-onset CRC survivors. Methods: We conducted a nationwide case-control study of 207 births in women with early-onset CRC and 1019 births in women without CRC from the general Swedish population (1992-2019), matched on age, calendar year of birth, parity, and county of residence. To control for genetic susceptibility and shared childhood exposures, we additionally identified 146 births in female siblings of the CRC survivors. Early-onset CRC cases were identified through the Swedish Cancer Register (1969-2019), and siblings were identified through the Swedish Multi-generation Register. Maternal characteristics and neonatal outcomes were retrieved from the Swedish Medical Birth Register and National Patient Register. Using conditional logistic regression, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: Compared to women without prior CRC, early-onset CRC survivors who gave birth had increased risk of pre-eclampsia (aOR 2.52, 95% CI 1.25 to 5.08), induced labor (aOR 1.64, 95% CI 1.09 to 2.46) and emergency Cesarean section (aOR 1.79, 95% CI 1.17 to 2.75), after adjustment for maternal education level, country of birth, body mass index and smoking in early pregnancy, and comorbidities. Sibling analyses showed similar trends, especially for higher risk of induced labor (aOR 2.58, 95% CI 1.03 to 6.49). Maternal history of early-onset CRC was also associated with offspring preterm birth (aOR 2.31, 95% CI 1.34 to 3.99) and low birth weight (aOR 2.95, 95% CI 1.40 to 6.21), and risks were particularly pronounced for medically indicated preterm birth (aOR 4.48, 95% CI 2.05 to 9.79). No significant associations were found for small for gestational age birth, low Apgar score, and congenital malformations. Conclusion: In this population-based study, history of early-onset CRC was associated with increased risk of adverse pregnancy outcomes, including pre-eclampsia, induction of labor, and emergency Cesarean section. Offspring to mothers with early-onset CRC also had increased risk of medically indicated preterm birth and neonatal low birth weight. Citation Format: Yin Cao, Stephanie Zhao, Tomas S. Bexelius, Jonas Söderling, Mengyao Shi, Bjorn Roelstraete, Barbara B. Warner, Olof Stephansson, Jonas F. Ludvigsson. Pregnancy and neonatal outcomes among early-onset colorectal cancer survivors: a nationwide case-control study. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P074.

Familial Reactive Perforating Collagenosis: Clinical, Dermoscopy, and Histopathological Features in Two Siblings

Transepidermal elimination disorders include reactive perforating collagenosis (RPC), perforating folliculitis, elastosis perforans serpiginosa, and Kyrle’s disease. RPC is a rare transepidermal elimination disorder wherein altered collagen is extruded through the epidermis. It has two types: rare inherited form and relatively common acquired form. Most inherited cases present during infancy or early childhood with papules on extensor surface of hands, elbows, knees preceded by superficial trauma. We report two female siblings of 11 and 10 years with multiple, symmetrically distributed, hyperpigmented papules with central keratotic plug, predominantly over extensor aspects of extremities with no aggravating and relieving factors. Clinical diagnosis of familial RPC was confirmed by consistent dermoscopic and histopathological findings. Both children were started on oral isotretinoin 10 mg/day with topical 12% ammonium lactate.

END-OF-LIFE EVENTS AND CAUSES OF DEATH IN DANISH LONG-LIVED FEMALE SIBLINGS

Abstract Long-lived siblings have better health and survival compared to “sporadic” long-lived individuals, but it is unknown whether they also differ in end-of-life events and causes of death. Deceased Danish long-lived female siblings (n=833, mean age at death=95.6) were identified through national health registers compared to controls matched on sex, year-of-birth, and year-of-death. End-of-life events (hospitalizations, emergency room visits, medication within the five years before death) and causes of death were analyzed using linear models with fixed effects and multinomial logistic models, respectively. End-of-life events and causes of death were not statistically significantly different between long-lived female siblings and “sporadic” long-lived individuals. However, long-lived female siblings presented non-significant higher risk of ischemic heart disease and cancer – and lower risk of mental diseases and accidents. The analyses will be extended to include men, a longer follow-up, and focus on dementia in the last years of life.

NOVEL GENOMIC AND EXCEPTIONAL LONGEVITY FINDINGS FROM THE LONG LIFE FAMILY STUDY

Abstract The Long Life Family Study (LLFS), funded by the National Institute on Aging, is an international collaborative study of the genetics and familial components of exceptional longevity and healthy aging. We phenotyped 4,953 individuals from 539 two-generational families (1,727 proband; 3,226 offspring) at baseline (2006-2009). A second visit (2014-2017) was conducted for 2,904 (478 proband; 2,426 offspring) participants. The longitudinal, comprehensive in-person visits measured domains of healthy aging, including physical performance, cognition, and blood markers. Extensive genetic analyses were performed using the baseline blood draw, including genotyping with the Illumina 2.5M Human Omni array, linkage analyses with the families, whole genome sequencing using the TopMED protocol, and metabolomic assays. Collectively, this symposium will present novel findings that examined differences in end of life events and cause of death between non-exceptional and exceptional long-lived women, elucidate potential rare variants associated with exceptional longevity, and examine new potential metabolomics pathways involved in gait speed and cardiovascular disease. Specifically, Dr. Galvin will share results from three Danish nationwide studies (including LLFS) on different end of life events in long-lived female siblings. Then, Dr. Gurinovich will share findings on new uncommon variants associated with extreme longevity. Next, Dr. Kuipers will discuss associations between lipid metabolomics and vascular health. Lastly, Dr. Santanasto will discuss lipid metabolomics associated with lower odds of slow gait speed. Dr. Evan Hadley, NIA, will be the discussant and will share insights and propose future directions for LLFS.

Epigenome-wide association study of short-term temperature fluctuations based on within-sibship analyses in Australian females

BackgroundTemperature fluctuations can affect human health independent of the effect of mean temperature. However, no study has evaluated whether short-term temperature fluctuations could affect DNA methylation. MethodsPeripheral blood DNA methylation for 479 female siblings of 130 families were analysed. Gridded daily temperatures data were obtained, linked to each participant’s home address, and used to calculate nine different metrics of short-term temperature fluctuations: temperature variabilities (TVs) within the day of blood draw and preceding one to seven days (TV 0–1 to TV 0–7), diurnal temperature range (DTR), and temperature change between neighbouring days (TCN). Within-sibship design was used to perform epigenome-wide association analyses, adjusting for daily mean temperatures, and other important covariates (e.g., smoking, alcohol use, cell-type proportions). Differentially methylated regions (DMRs) were further identified. Multiple-testing comparisons with a significant threshold of 0.01 for cytosine-guanine dinucleotides (CpGs) and 0.05 for DMRs were applied. ResultsAmong 479 participants (mean age ± SD, 56.4 ± 7.9 years), we identified significant changes in methylation levels in 14 CpGs and 70 DMRs associated with temperature fluctuations. Almost all identified CpGs were associated with exposure to temperature fluctuations within three days. Differentially methylated signals were mapped to 68 genes that were linked to human diseases such as cancer (e.g., colorectal carcinoma, breast carcinoma, and metastatic neoplasms) and mental disorder (e.g., schizophrenia, mental depression, and bipolar disorder). The top three most significantly enriched gene ontology terms were Response to bacterium (TV 0–3), followed by Hydrolase activity, acting on ester bonds (TCN), and Oxidoreductase activity (TV 0–3). ConclusionsShort-term temperature fluctuations were associated with differentially methylated signals across the human genome, which provides evidence on the potential biological mechanisms underlying the health impact of temperature fluctuations. Future studies are needed to further clarify the roles of DNA methylation in diseases associated with temperature fluctuations.

Exploring female siblings as social media influencers in the Arab World

This paper aims to explore a new phenomenon sweeping across the Arab World of female sibling social media influencers. Social media influencers are well known for having started as informed bloggers and social networkers. They built for themselves an aura of authority in certain areas thus attracting people to follow them; some of their followers become fans. This paper will give an overview of the phenomenon of female sibling social media influencers, drawing upon the case study of a number of examples of female sibling social media influencers from the Arab World. It will look at why this is an important phenomenon, how female social media influencers behave online and the common characteristics they have. This paper is of exploratory nature and draws the attention to a growing phenomenon worth exploring and researching further. The paper identifies a number of potential areas and opportunities for future research.

CEO birth order and corporate social responsibility behaviors: The moderating effect of female sibling and age gap.

Corporate social responsibility (CSR) is one of the most important business strategies which helps enterprises obtain competitive advantage and improve performance. Scholars have conducted many beneficial studies on the driving factors of CSR behaviors from the perspective of CEO traits, but rarely focus on the impact of the CEO's early family experiences. This study aims to fill this research gap by investigating the influence of CEO birth order on firms' CSR behaviors, and further exploring the possible moderating effects of the presence of a female sibling and the age gap between the CEO and the closest sibling. This study takes Chinese non-financial private listed companies from 2010 to 2017 as the research samples, and empirically tests the relationship between CEO birth order and a firm's CSR behaviors. The empirical results show that CEO birth order negatively influences corporate social responsibility behaviors, and this relationship would be weakened when the CEO has a female sibling or the age gap between CEO and the closest sibling is larger. This paper extends the research on personal family factors from the field of social psychology to the business field and finds a new driving factor of corporate social responsibility behavior from the perspective of the CEOs' early family factors.

Same-Sex Marriage and Common Mental Health Diagnoses: A Sibling Comparison and Adoption Approach

ABSTRACT We aimed to test whether the association between same-sex marriage and common mental health diagnoses was explained by shared genetic and environmental familial influences using sibling comparison and adoption analyses. For the sibling comparison analysis, participants (1,177,712 men and 1,266,917 women) were individuals born in Sweden between 1932 and 1994 and had ever been recorded as married (in opposite-sex or same-sex marriages). For the adoption analysis, participants were 147,164 and 1,298 female–female full sibling and adoptive sibling pairs, respectively. Based on medical records, prescribed medication, and death certificates, depression, substance abuse, and suicide (completed and attempted) from age 18 years were identified. For both sexes, being in a same-sex marriage was associated with greater risk of depression, substance abuse, and suicide, compared with being in an opposite-sex marriage. Controlling for shared familial confounding reduced this difference by less than 20% in magnitude, but overall mental health disparities for individuals in same-sex marriages remained statistically significant. Among women, only the genetic correlation between same-sex marriage and depression was statistically significant (r = .33). Same-sex marriage, as a proxy for sexual orientation, was associated with increased risk of certain mental health diagnoses and shared familial confounding explained a small component of this association, depending on the diagnosis. The findings indicate that sexual orientation disparities in mental health outcomes may involve unmeasured factors, and a relatively small proportion should be considered that may be due to shared familial confounding relevant to both sexual orientation and psychopathology.

Caspase-10 affects the pathogenesis of primary biliary cholangitis by regulating inflammatory cell death

Primary biliary cholangitis (PBC) is an autoimmune disease that involves chronic inflammation and injury to biliary epithelial cells. To identify critical genetic factor(s) in PBC patients, we performed whole-exome sequencing of five female siblings, including one unaffected and four affected sisters, in a multi-PBC family, and identified 61 rare heterozygote variants that segregated only within the affected sisters. Among them, we were particularly interested in caspase-10, for although several caspases are involved in cell death, inflammation and autoimmunity, caspase-10 is little known from this perspective. We generated caspase-10 knockout macrophages, and then investigated the obtained phenotypes in comparison to those of its structurally similar protein, caspase-8. Unlike caspase-8, caspase-10 does not play a role during differentiation into macrophages, but after differentiation, it regulates the process of inflammatory cell deaths such as necroptosis and pyroptosis more strongly. Interestingly, caspase-10 displays better protease activity than caspase-8 in the process of RIPK1 cleavage, and an enhanced ability to form a complex with RIPK1 and FADD in human macrophages. Higher inflammatory cell death affected the fibrotic response of hepatic stellate cells; this effect could be recovered by treatment with UDCA and OCA, which are currently approved for PBC patients. Our findings strongly indicate that the defective roles of caspase-10 in macrophages contribute to the pathogenesis of PBC, thereby suggesting a new therapeutic strategy for PBC treatment.

Germ Cell Tumour in Male and Female Siblings: A Case Report and Literature Review

Germ Cell Tumour in Male and Female Siblings: A Case Report and Literature Review

A whole genome sequencing approach to anterior cruciate ligament rupture-a twin study in two unrelated families.

Predisposition to anterior cruciate ligament (ACL) rupture is multi-factorial, with variation in the genome considered a key intrinsic risk factor. Most implicated loci have been identified from candidate gene-based approach using case-control association settings. Here, we leverage a hypothesis-free whole genome sequencing in two two unrelated families (Family A and B) each with twins with a history of recurrent ACL ruptures acquired playing rugby as their primary sport, aimed to elucidate biologically relevant function-altering variants and genetic modifiers in ACL rupture. Family A monozygotic twin males (Twin 1 and Twin 2) both sustained two unilateral non-contact ACL ruptures of the right limb while playing club level touch rugby. Their male sibling sustained a bilateral non-contact ACL rupture while playing rugby union was also recruited. The father had sustained a unilateral non-contact ACL rupture on the right limb while playing professional amateur level football and mother who had participated in dancing for over 10 years at a social level, with no previous ligament or tendon injuries were both recruited. Family B monozygotic twin males (Twin 3 and Twin 4) were recruited with Twin 3 who had sustained a unilateral non-contact ACL rupture of the right limb and Twin 4 sustained three non-contact ACL ruptures (two in right limb and one in left limb), both while playing provincial level rugby union. Their female sibling participated in karate and swimming activities; and mother in hockey (4 years) horse riding (15 years) and swimming, had both reported no previous history of ligament or tendon injury. Variants with potential deleterious, loss-of-function and pathogenic effects were prioritised. Identity by descent, molecular dynamic simulation and functional partner analyses were conducted. We identified, in all nine affected individuals, including twin sets, non-synonymous SNPs in three genes: COL12A1 and CATSPER2, and KCNJ12 that are commonly enriched for deleterious, loss-of-function mutations, and their dysfunctions are known to be involved in the development of chronic pain, and represent key therapeutic targets. Notably, using Identity By Decent (IBD) analyses a long shared identical sequence interval which included the LINC01250 gene, around the telomeric region of chromosome 2p25.3, was common between affected twins in both families, and an affected brother’. Overall gene sets were enriched in pathways relevant to ACL pathophysiology, including complement/coagulation cascades (p = 3.0e-7), purine metabolism (p = 6.0e-7) and mismatch repair (p = 6.9e-5) pathways. Highlighted, is that this study fills an important gap in knowledge by using a WGS approach, focusing on potential deleterious variants in two unrelated families with a historical record of ACL rupture; and providing new insights into the pathophysiology of ACL, by identifying gene sets that contribute to variability in ACL risk.

Two Sisters were Diagnosed with Childhood Systemic Lupus Erythematous

We are herein reporting two female siblings with childhood-onset Systemic Lupus Erythematosus (SLE). The children were diagnosed as having SLE in reverse birth order at ages 2 and 6 years. Younger sister's initial symptoms were serositis, proteinuria, and hemolytic anemia with laboratory findings of hypocomplementemia and positive ANA/anti-dsDNA antibody. After 18 months, the older sister presented with high-grade fever, arthralgia proteinuria, oral mucous ulcer, butterfly rash, and positive ANA/anti-dsDNA antibody.

CT-132 Outcome of Sex-Mismatched Allogeneic Hemopoietic Stem Cell Transplantation from Human Leukocyte Antigen–Identical Sibling Donors in Patients With Hematologic Diseases

Hematopoietic stem cell transplantation is a procedure aiming to cure hematologic diseases. However, graft-versus-host disease (GVHD) and disease relapse/failure are common side effects of this treatment. Sex-mismatched transplantation, particularly with female donors and male patients, is known to be associated with higher incidence of GVHD or lower incidence of survival. This is caused by the antibodies against minor histocompatibility antigens found on the Y chromosome of the male recipient, which were found to be associated with increased risk of chronic GVHD and non-relapse mortality. The study aimed to determine the incidence of acute and chronic GVHD, overall survival, and non-relapse mortality when male patients received stem cells from female matched sibling donors in allogeneic hematopoietic stem cell transplantation. Retrospective study over 8 years. Nasser Institute Hospital. In this study, patients were divided into 2 groups. Group 1: female donors to male patients (245 patients). Group 2: male donors to female patients (186 patients) and same-sex donors and patients (506 patients). The median age was 20 years (7 months-60 years). The outcome of transplants in the female-to-male group was compared with that of the male-to-female and same-sex group. Overall survival, incidence of acute and chronic GVHD, non-relapse mortality, and relapse/failure rate. Overall survival was 68.6% in group 1 compared to 69.5% in group 2 (P=0.5). Acute GVHD was 24% in group 1 compared to 19.6% in group 2 (P=0.1). Chronic GVHD was 15.1% in group 1 compared to 9.6% in group 2 (P=0.02). Non-relapse mortality was 27.7% in group 1 compared to 25.7% in group 2 (P=0.5). Relapse/failure rate was 4.9% in group 1 compared to 6.5% in group 2 (P=0.3). Allogeneic stem cell transplantation for male patients from female donors can be associated with a significantly higher rate of chronic GVHD but a lower incidence of relapse/failure.

P.167 Clinical outcome study of dysferlinopathy: gait analysis of siblings and phenotype variation

Patients with limb girdle muscular dystrophy (LGMD) R2/2B, caused by mutations in the <i>DYSF</i> gene, have a distinct gait pattern, although this has not been characterised with instrumented gait analysis. In the Jain Foundation Clinical Outcome Study of dysferlinopathy (COS2, http://www.jain-foundation.org/dysferlinoutcomestudy), we are investigating the utility of instrumented gait analysis as a novel clinical biomarker. Patients with LGMDR2 have variability in the presentation of muscle weakness and rate of progression, even within family members. In a pair of siblings with LGMDR2, we conducted gait analysis at two points, six months apart when barefoot and shod. The aim was to quantify gait in siblings with LGMDR2 and evaluate temporospatial parameters changes over six months. Two COSII patients, a male aged 30, and his younger sister aged 27, completed gait analysis at baseline and six-month visits using an instrumented walkway (GAITRite, 240Hz). Patients were asked to walk at a comfortable walking speed when barefoot and shod, and to walk fast when shod only. Temporospatial characteristics including gait velocity, step length, step width, stance and swing duration were extracted. Barefoot gait velocities at baseline were similar between siblings with the male walking at 1.16m/s and his sister at 1.20m/s, however the male sibling walked with a step width double that of his sister. Functionally the male had a more severe disease presentation, with a North Star assessment for limb girdle type muscular dystrophy score of 28/54 at baseline, and the female 42/54. At baseline, both siblings had capacity to increase shod walking speed when asked to walk fast; by 25% for the male and 47% for the female sibling. At six months when shod, gait analysis determined very small changes (<5%) in walking speed, step length, stance time in both siblings. However, step width increased by 12% in the male subject. Gait analysis provides detailed evaluation of temporospatial parameters and captures differences across siblings and walking conditions.

Correlation between novel compound heterozygous ADAMTSL4 variants and primary phenotypes of ectopia lentis et pupillae

PurposeTo investigate molecular pathogenesis of congenital ectopia lentis accompanied by various ophthalmic manifestations in a pedigree. MethodsThree female siblings, their spouse and offspring underwent ophthalmic and general medical examinations. Genetic variants were screened with the whole exome sequencing and analyzed in either a dominant or recessive inheritance manner. Gene mutations were ascertained with the Sanger sequencing after the polymerase chain reaction. ResultsAll three female siblings were diagnosed as the Ectopia lentis et pupillae (ELeP) through combination of clinical examination and genetic analysis. No characteristic pathological changes of skeletal, metabolic and cardiac abnormalities were observed. Thirteen genetic variants were selected out through analyzing in the dominant or recessive inheritance manner, but they were not associated with EL. Among them, ALOX15B variant may explain the skin disease in this pedigree. After inspection the known genes related to EL, novel compound heterozygous mutations (p.Ser264LeufsX37/p.Gly757ValfsX62) in ADAMTSL4 were discreetly identified in this ELeP pedigree. ConclusionsNovel compound heterozygous ADAMTSL4 variants are responsible for ELeP in the current pedigree. Correlation between ADAMTSL4 variants and ELeP was firstly established based on our 12 years follow-up studies and previous reports of ELeP and of ADAMTSL4–related eye disorders. The primary phenotypes caused by ADAMTSL4 variants include EL, EP, poor pupillary dilation, and axial elongation. Highly varying phenotypes including glaucoma, high myopia retinapathy, and poor vision and so on may be the secondary impairments. All these secondary impairments may be improved if proper clinical interventions are implemented in time.

Silent witnesses: the experience of having a sibling with anorexia nervosa

BackgroundThis study explored the experience of having a sibling with anorexia nervosa and the sibling perspectives on service provision.MethodFour focus groups were conducted with 14 siblings (8 female, 6 male, age 11–19 years) of adolescents with anorexia nervosa or related restrictive eating disorders. Group discussions were transcribed and analysed using thematic analysis.ResultsFour themes and eight sub-themes were generated. These illustrated siblings feel greatly affected by the way the family needs to change to support someone with anorexia nervosa. Feelings of ambivalence and acceptance were also evident. They described silencing their own emotions and needs so as not to trouble others, and distancing themselves from their families in order to cope. Some female (but no male) siblings identified an impact on their own perceptions of eating and body image. Siblings generally felt that services had not attended to their needs, and that they had not been appropriately included in treatment.ConclusionsData from this study suggest the sibling experience needs to be more carefully considered and included in treatment. This may include a more explicit invitation to sessions and a more active discussion about their own needs and useful involvement in treatment sessions. Findings point to ways siblings may be better supported, such as peer support groups.

Caregiving roles of female guardians, older siblings, and time spent on child activities

AbstractObjectiveThis pilot study investigated the different roles Zambian guardians and older siblings play in stimulating children and how time spent engaging in child stimulating activities was associated with child stimulation. In this study, guardians were women who are primary caregivers of the children.BackgroundA lot of research has been done on child stimulation but little is known of different roles caregivers, especially older siblings, play in child stimulation.MethodQuestionnaires were administered to caregivers (both older siblings and guardians) of children between 3 and 5 years of age and their older siblings above 7 years old.ResultsResults showed that despite the female guardians spending more time taking care of their children, older siblings were significantly more involved in child stimulating activities than the female guardians. Further data showed that guardians with more education were associated with increased child stimulation. However, socioeconomic status, age of guardians, and family size were not associated with child stimulation.ConclusionIn poor communities, older siblings engage more in child stimulating activities than their guardians. Child stimulation interventions have often focused on parents (guardians) leaving out older siblings who may play a more critical role, especially in circumstance were parental care and availability are absent. Therefore, for child cognitive and socioemotional stimulation interventions to be more effective in poor communities, they should include siblings. More research is needed to understand the role of male guardians and the degree to which sibling stimulation predicts cognitive and socioemotional development.