Israeli Arab Family Research Articles

Genetic correction of TRMU allele restored the mitochondrial dysfunction-induced deficiencies in iPSCs-derived hair cells of hearing-impaired patients.

Sensorineural hearing loss often results from damaged or deficient inner ear hair cells. Mitochondrial 12S rRNA 1555A>G mutation has been associated with hearing loss in many families. The m.1555A>G mutation is a primary factor underlying the development of hearing loss and TRMU allele (c.28G>T, p.Ala10Sser) encoding tRNA thiouridylase interact with m.1555A>G mutation to cause hearing loss. However, the tissue specificity of mitochondrial dysfunction remains elusive and there is no highly effective therapy for mitochondrial deafness. We report here the generation of induced pluripotent stem cells (iPSCs) from lymphoblastoid cell lines derived from members of an Arab-Israeli family (asymptomatic individual carrying only m.1555A>G mutation, symptomatic individual bearing both m.1555A>G and c.28G>T mutations, and control subject). The c.28G>T mutation in iPSC lines from a hearing-impaired subject was corrected by CRISPR/Cas9. These iPSCs were differentiated into otic epithelial progenitor (OEP) cells and subsequent inner ear hair cell (HC)-like cells. The iPSCs bearing m.1555A>G mutation exhibited mildly deficient differentiation into OEP and resultant HC-like cells displayed mild defects in morphology and electrophysiological properties. Strikingly, those HC-like cells harboring m.1555A>G and TRMU c.28G>T mutations displayed greater defects in the development, morphology and functions than those in cells bearing only m.1555A>G mutation. Transcriptome analysis of patients-derived HC-like cells revealed altered expressions of genes vital for mechanotransduction of hair cells. Genetic correction of TRMU c.28G>T mutation yielded morphologic and functional recovery of patient derived HC-like cells. These findings provide new insights into pathophysiology of maternally inherited hearing loss and a step toward therapeutic interventions for this disease.

Examining the mediating effect of psychosocial resources on the relationship between ambivalent feelings and depression among Israeli Arab family caregivers of people with dementia.

Providing care for family members of individuals with dementia can be accompanied by a myriad of emotions, usually involving negative as well as positive feelings, or "ambivalent feelings." Recent studies conducted among family caregivers of people with dementia have shown ambivalent feelings to be associated with serious psychological consequences, such as increased depression. However, little is known about the path leading from ambivalent feelings to depression. Thus, the aim of this study was to examine the interplay of ambivalent feelings and depression with family caregivers' psychosocial resources-that is, their coping strategies and social support. A cross-sectional study using face-to-face interviews (via structured questionnaire) was conducted with 175 Israeli Arab family caregivers (adult children and spouses) of elderly people with Alzheimer's disease (87.4% female; 72% adult children; mean age = 54.28). Overall, the participants reported a mild level of depression (mean = 7.93; SD = 4.30; range 0-15) and a moderate level of ambivalent feelings (mean = 1.63; SD = 1.04; range 0-3). Additionally, as expected, ambivalent feelings made a unique-although modest-contribution, adding an additional 6% (p < 0.001) to the explanation of depression (R2 = 0.56, p<0.001). Whereas, neither problem-focused coping nor emotion-focused coping played a significant role in mediating the relationship between ambivalent feelings and depression, social support did mediate the relationship between these variables. Our findings show that strengthening and expanding social networks among Israeli caregivers of people with Alzheimer's disease can minimize the impact of experiences of emotional feelings on depression.

Prothrombin “Carmel”: Identification of a Novel Homozygous Mutation in the Prothrombin Gene Causing Coagulation Factor II Deficiency and Inherited Bleeding Disorder in an Israeli Arab Family

Congenital prothrombin deficiency, also known as hypoprothrombinemia is a rare autosomal recessive disorder characterized by severe bleeding manifestations and decreased prothrombin antigen levels below 10% activity of normal. Dysprothrombinemia, which is characterized by normal antigen levels but a dysfunctional prothrombin molecule, shows a more variable level in bleeding tendency, and there is often a good correlation between the levels of prothrombin activity and clinical severity. We have studied a large consanguineous family of thirteen members contains two patients with a prolonged protrombine time (PT) and activated partial thromboplastin time (aPTT) with prothrombin activity of 11%. DNA was isolated from leukocytes and the thrombin exons were amplified by polymerase chain reaction and sequenced. Exon 14 revealed a point mutation in the codon of Tyrosine 560 which is substituted by Histidine (Tyr560His). Mutation at this residue most probably distorts the structure of the peptidase catalytic domain. The variation segregated as expected in the family, it did not appear in dbSNP, EVS or the 1000 genome project. Further investigation is needed to determine the antigen level and to elucidate the potential effect of the mutation on the structure and the activity of the enzyme. This prothrombin is designated as Prothrombin “Carmel”. DisclosuresNo relevant conflicts of interest to declare.

The mediating effect of social support and coping strategies on the relation between family stigma and caregiver burden among Israeli Arab family caregivers of people with Alzheimer’s disease (AD)

Objectives Many studies have attempted to identify the factors that are associated with caregiver burden among family caregivers of people with Alzheimer’s disease (AD), because of its plethora of negative consequences. One unique factor that has been investigated recently is family stigma. However, the path leading from family stigma to caregiver burden has not been thoroughly studied. Hence, this study had two main objectives. The first was to examine whether family stigma was a predictor of caregiver burden among Israeli Arab family caregivers of a person with AD. The second was to examine the interplay of family stigma and caregiver burden with coping strategies and social support. Methods Structured face-to-face interviews were conducted with 175 Israeli Arab family caregivers (adult children and spouses) of elderly people with AD (87.4% female; 71.4% adult children; mean age = 54.28). Results Overall, the participants reported moderate levels of caregiver burden and family stigma. Additionally, as expected, family stigma made a unique – although modest – contribution to the explanation of caregiver burden. Whereas neither problem-focused coping nor emotion-focused coping played a significant role in mediating the relation between family stigma and caregiving burden, social support did mediate the relation between these variables. Conclusions Our findings reveal how social support is important as a specific way to reduce the impact of family stigma on caregiver burden.

Parental Behaviors and Involvement in Children’s Digital Activities among Israeli Jewish and Arab Families during the COVID-19 Lockdown

ABSTRACT Research Findings: The study explored everyday parenting behaviors and their relations to parents’ involvement in their children’s digital activities during the COVID-19 lockdown, among Israeli Jewish and Arab parents of young children. We studied parents’ behaviors through the prism of the Parenting Pentagon Model (PPM), which integrates five constructs of daily parenting behaviors that are beneficial for children’s development: Partnership between the caretakers, Parental Leadership, Love Behaviors, Encouraging Independence, and Adherence to Rules. Participants, 487 parents (290 Jewish and 197 Arab) of children (2-to-8-years-old) answered questionnaires. Findings showed that both Jewish and Arab parents reported that Love behaviors were most frequent during the lockdown, followed by Leadership. Encouragement of Independence, adherence to Rules and Partnership were less frequent. Additionally, the more parents behaved beneficially in their daily life (according to PPM), the more they were involved in their child’s digital activities, beyond family background (child’s age, parent’s education, and family’s size). Practice or Policy: The results can assist in planning support programs for parents during times of crisis. Parental guidance regarding beneficial parenting and advantageous involvement in children’s digital activities may be more helpful than restrictions and warnings regarding the risk of young children’s exposure to digital activities and screens.

First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery

A high rate of consanguinity leads to a high prevalence of autosomal recessive disorders in inbred populations. One example of inbred populations is the Arab communities in Israel and the Palestinian Authority. In the Palestinian Authority in particular, due to limited access to specialized medical care, most patients do not receive a genetic diagnosis and can therefore neither receive genetic counseling nor possibly specific treatment. We used whole-exome sequencing as a first-line diagnostic tool in 83 Palestinian and Israeli Arab families with suspected neurogenetic disorders and were able to establish a probable genetic diagnosis in 51% of the families (42 families). Pathogenic, likely pathogenic or highly suggestive candidate variants were found in the following genes extending and refining the mutational and phenotypic spectrum of these rare disorders: ACO2, ADAT3, ALS2, AMPD2, APTX, B4GALNT1, CAPN1, CLCN1, CNTNAP1, DNAJC6, GAMT, GPT2, KCNQ2, KIF11, LCA5, MCOLN1, MECP2, MFN2, MTMR2, NT5C2, NTRK1, PEX1, POLR3A, PRICKLE1, PRKN, PRX, SCAPER, SEPSECS, SGCG, SLC25A15, SPG11, SYNJ1, TMCO1, and TSEN54. Further, this cohort has proven to be ideal for prioritization of new disease genes. Two separately published candidate genes (WWOX and PAX7) were identified in this study. Analyzing the runs of homozygosity (ROHs) derived from the Exome sequencing data as a marker for the rate of inbreeding, revealed significantly longer ROHs in the included families compared with a German control cohort. The total length of ROHs correlated with the detection rate of recessive disease-causing variants. Identification of the disease-causing gene led to new therapeutic options in four families.

An ancestral variant causing type I xanthinuria in Turkmen and Arab families is predicted to prevail in the Afro-Asian stone-forming belt.

Classical xanthinuria is a rare autosomal recessive metabolic disorder characterized by lack of xanthine dehydrogenase activity that often manifests as xanthine urolithiasis and risk of drug toxicity. Variants in the XDH or HMCS gene underlie classical xanthinuria type I and type II, respectively. Here we present two Israeli Arab families affected by type I xanthinuria in whom a c.2164A>T (Lys722Ter) variant in the XDH gene, previously reported in a Turkish family of Turkmen origin, was identified. Analysis of polymorphic markers surrounding the variant site revealed common haplotypes spanning 0.6 Mbp shared by all three, and 1.7 Mbp shared by two of the studied families. By applying Bayesian methods to a simple model of crossover events through generations in the chromosomes carrying the variant, the most recent common ancestor of these families was found to be 179 (95% credible limit 70) generations old. The estimated antiquity of the variant, the historical genealogy of the affected families and the history and present day dispersion of their people strongly suggest prevalence of this variant in the Afro‐Asian stone‐forming belt. As far as we are aware, this is a first report of an ancient variant causing xanthinuria with potential wide geographical dispersion.

Problematic Internet use in Israeli-Arab adolescent males: Do parenting styles matter?

The current study explored the relationships between parenting styles and problematic internet use (PIU) in male adolescents from Israeli-Arab families. In the research literature, little is known about the role played by parenting in relation to children’s PIU in Arab societies. One hundred and eighty male adolescents whose age ranges from 12 to 16 (M = 13.92, SD = 1.42) reported their internet behavior and their parents’ parenting styles. Controlling for the participants’ age, family size, and grades, parenting styles explained 24% of the variance in PIU scores, with authoritarian parenting being the only significant unique predictor. A further analysis of covariance revealed that adolescents who perceived their parents as authoritative scored lower than their counterparts in PIU. Our findings suggest that while Israeli-Arab male adolescents might benefit from authoritative parenting at home, it is the parental authoritarian practices and behaviors per se that should be targeted as part of PIU intervention and prevention efforts.

Who internalizes courtesy stigma and how? A study among Israeli Arab family caregivers of persons with dementia

Objectives: The expected rise in the number of persons with dementia is accompanied by an increasing interest in understanding and reducing the stigmatic beliefs experienced by family caregivers of persons with the disease. While researchers have recently distinguished between family caregivers’ perceptions of public stereotypes (i.e., courtesy stigma) and the internalization of these perceptions (i.e., affiliate stigma), no study has yet assessed the characteristics of dementia caregivers who internalize courtesy stigma and how they do so. The aim of this study was to examine the characteristics of family caregivers of persons with dementia who internalize courtesy stigma, and to investigate this internalization process.Method: Structured face-to-face interviews were conducted with 175 Israeli Arab family caregivers (87.4% female; 71.4% adult children; mean age = 54.28) for persons with Alzheimer’s disease.Results: Overall, half of the participants reported experiencing affiliate stigma as a result of taking care of a relative with dementia. Regression analyses showed that lower educational level, increased courtesy stigma and lower levels of social support were the main predictors of affiliate stigma. Social support partially mediated the association between courtesy and affiliate stigma.Conclusion: Our findings provide important insights for the conceptual understanding and the development of interventions to reduce stigma among family caregivers of persons with dementia.

Convergent validity and reliability of the Hebrew version of the Parenting Styles and Dimensions Questionnaire (PSDQ) in Hebrew-speaking Israeli-Arab families

The study examined the convergent validity and reliability of the Hebrew-translated 32 items of the Parenting Styles and Dimension Questionnaire (PSDQ) among Israeli-Arab families, who speak Hebrew as their second language. 187 adolescents (116 boys; 64 girls; 7 participants did not report their sex) and one of their parents (106 fathers; 81 mothers) completed the PAQ and the PSDQ (respectively). Subject to two exceptions (alphas below .60), the instrument’s scales exhibited an acceptable internal consistency (.64 ≤ α ≤ .89) and good convergence with the PAQ scales (with mid- to large-size correlations). Taken together, the findings suggest that the PSDQ in its Hebrew version could be acceptable for assessing parenting styles among literate Hebrew-speaking populations. The limitations and implications concerning this conclusion are discussed, along with some cultural aspects.

Physical Activity Among Israeli-Arab Adolescent Males: How Do Parenting Styles Matter?

Physical activity contains many benefits for adolescents’ physical and mental health, and also for building healthy living routines and habits for the future. The current study examined the associations between parenting styles and adolescents’ physical activity among Israeli-Arab families of male adolescents, in seeking to boost the limited information on this most important topic. Participants consisted of 177 male Israeli-Arab adolescents (M = 13.93, SD = 1.42) with normal weight. Controlling for the participants’ age, weight, and grades in school, parenting styles explained about 30% of the variance in the participants’ reports of their physical activity, with the authoritative and authoritarian parenting inversely correlated with the latter variable. Adolescents who perceived their parents as authoritative were reportedly more physically active than their counterparts who perceived their parents as authoritarian. In common with previous studies, the findings suggest that authoritative parenting may be a cross-culturally preferable style in fostering a desired physical activity rate among adolescents.

Families raising a child with disability – Social and cultural and political considerations: Israeli Jewish and Arab Families

Social, political, and cultural realities have an effect on all members of society. For families with a child with disability there are additional challenges. Being a minority family with a child with a disability adds to the challenges. This study compares the family quality of life (FQOL) of families with a child with disability in Jewish and Arab communities in Israel. Main caregivers of children with disabilities of 158 Jewish and 105 Arab Israeli responded to the Family Quality of Life Survey, which operationalizes FQOL as a construct of six measurement dimensions in nine core family life domains. Overall, Jewish families in Israel reported higher FQOL than Arab families. Although eight of the nine domains were rated highly for Importance, the main outcome measures Attainment and Satisfaction were rated lower for almost all domains. Some domains contributed to overall differences more than others. The patterns also differed for the Jewish and Arab families. Social/cultural/political status of families are important for policy and practice professionals to consider as having possible impact on the family of a child with a disability. Further research is needed to develop application models for addressing the needs of minority populations in designing programs into the general service delivery system.

Coherence of Representations Regarding the Child, Resolution of the Child's Diagnosis and Emotional Availability: A Study of Arab-Israeli Mothers of Children with ASD.

This study examined the interplay of mothers' coherent representations of their child (i.e., multidimensional and balanced view); resolution of the child's ASD diagnosis (i.e., acceptance); and emotional availability to the child in the unique cultural context of Arab-Israeli families. Participants were 46mothers and their 2-8year old sons. Coherent representations and resolution of the diagnosis were assessed using narrative measures. Emotional availability (namely, sensitivity, structuring, and lack of intrusiveness and hostility) was observed during mother-child play interactions. Results suggested that coherent and resolved mothers were more emotionally available than incoherent and/or unresolved mothers. These findings highlight the importance of supporting mothers' ability to accept the child's diagnosis and see the unique characteristics of the child beyond his ASD symptoms.

Continuity in literacy achievements from kindergarten to first grade: a longitudinal study of Arabic-speaking children

The study addressed the question of continuity in literacy achievements from kindergarten to first grade among Arabic-speaking children in Israel. We examined (1) how age and family socio-economic status (SES) predict children’s literacy skills in kindergarten and (2) how age, SES, and early literacy skills in kindergarten predict literacy achievements in first grade. This examination is interesting due to the diglossic nature of the Arabic language and the low SES level of Israeli Arab families on one hand, and the transparent pointed Arabic script on the other hand. Literacy skills of 109 children were assessed in kindergarten and 1 year later in first grade. Path analysis showed that children’s age and family SES had a direct significant effect on children’s early literacy skills. Furthermore, children’s early literacy skills had significant direct effects on literacy achievements in first grade. SES had a direct effect on phonological awareness and word reading in first grade, but only an indirect effect on text reading. Children’s age in kindergarten had an indirect effect through early literacy skills on literacy achievements in first grade. Beyond the prediction of early literacy skills to achievements in first grade, the results highlight the unique role of child’s age and family SES, which continue to affect child’s literacy achievements in first grade in spite of formal teaching and the highly transparent pointed Arabic script. The results are discussed and educational recommendations are suggested.

Whole Exome Sequencing In Arab And Jewish Israeli Families Multiply Affected With Schizophrenia

Background Schizophrenia is a complex disorder that likely results from the impact of both common and rare susceptibility variants. The impact of common variants with small effect in schizophrenia has been widely investigated. After large scale sequencing studies in schizophrenia become feasible, multiple whole exome sequencing studies were performed, and found disruptive mutations distributed across many different genes. They also identified gene sets with enrichment of rare variants with large effect. Sequencing studies performed in large families have showed that candidate variants did not necessarily segregate within the families, and were different in each family. To search for inherited variants of large effect we performed whole exome sequencing in Arab and Jewish Israeli families multiply affected with schizophrenia. All the Jewish families were of non-Ashkenazi origin. The Arab families were drawn from an ethnically homogenous population with an unusually high level of consanguinity, and a low rate of intermarriage with other population groups in Israel. Methods Eight large families with multiple subjects affected with schizophrenia were selected, since in these families the genetic transmission appears to be most consistent with inheritance of highly-penetrant disease alleles. In total whole exome sequencing and data analysis of 32 family members were performed. Each family was analyzed separately, first according to the most appropriate single-gene mode of inheritance and second according to an oligogenic mode of inheritance looking for all variants shared between affected family members. Multiple variants found by applying the oligogenic mode of inheritance were prioritized by using the VarElect software. To assess enrichment of rare segregating variants in specific genes in the schizophrenia cases, we performed a gene-based collapsing dominant model analysis while correcting for population stratification. Permutation-based analyses were done to test for enrichment of previously detected de-novo variants and additional candidate gene sets. Results We were able to identify several interesting rare segregating functional variants. Single-gene inheritance candidates which are consistent with the most appropriate mode of inheritance in a given family were found in only 2 out of 8 analyzed families. These variants were found in DOCK8 and DRP2 genes. No gene reached genome-wide significance in the collapsing analysis. An enrichment of variants in candidate gene sets is currently under investigation. Discussion It seems that schizophrenia in most of these families arises from the combined effects of several different coding variants, even in ethnically homogenous consanguineous Arab Israeli families.

Social and Cultural Considerations in Family Quality of Life: Jewish and Arab Israeli Families' Child‐Raising Experiences

AbstractThis paper compares the family quality of life (FQOL) of families with a child with disability in Jewish and Arab communities in Israel. Social, political, and cultural realities have an effect on all members of society. For families with a child with disability there are additional challenges. Being a minority family with a child with a disability adds to the challenges. One hundred fifty‐eight Jewish and 105 Arab Israeli caregivers of children with disabilities responded to the Family Quality of Life Survey (FQOLS‐2006), which operationalizes FQOL as a construct of six measurement dimensions in nine core family life domains. Overall, Jewish families in Israel reported higher FQOL than Arab families. Although eight of the nine domains were rated highly for Importance, the main outcome measures Attainment and Satisfaction were rated lower for almost all domains. Some domains contributed to overall differences more than others. The patterns also differed for the Jewish and Arab families. It is important for policy and practice to consider the social/political status of families and to consider the possible impact this has on the family of a child with a disability. Further research is needed to develop application models for addressing the needs of minority populations in designing programs into the general service delivery system.

Exploring family stigma among caregivers of persons with Alzheimer's disease: The experiences of Israeli-Arab caregivers.

Providing care to persons with Alzheimer's disease poses challenges for spouses and adult children, including experiencing stigmatic beliefs towards themselves-i.e., family stigma. Drawing on the frameworks of ethnicity and stigma and ethnicity and dementia, the current study explored stigmatic experiences among Israeli Arab family caregivers of a person with Alzheimer's disease. Three focus groups with 20 caregivers (adult children and spouses) of persons with Alzheimer's disease were conducted. Data were analyzed using theory-led thematic analysis. Caregivers reported experiencing family stigma in two dimensions: public and affiliate stigma, in both the existence of an attribution process in which cognitive stereotypes elicit negative and positive emotions which in turn provoke behavioral attributions, was evident. Family stigma was found to be a discernible feature of everyday reality among Israeli Arab caregivers of persons with Alzheimer's disease and stress the importance of developing management strategies that are tailored to the socio-cultural characteristics of the caregivers.

‘Everything comes with a price … ’; family language policy in Israeli Arab families in mixed cities

ABSTRACTThe state of Israel has an indigenous minority of Arabs, distinguished from the Jewish majority by national, religious, cultural, and linguistic characteristics. Most Jews use Hebrew as their L1, while Arabs use Arabic, both official languages in Israel. Most Arabs tend to live in separate geographical areas and about 10% of Israel’s Arabs live in ‘mixed cities.’ Since neither side defines them as homogeneous, these cities may afford rich insights about Israeli reality. Recently, there has been a growing tendency among Arab parents in mixed cities to send their children to Hebrew-speaking educational settings, especially in preschool years. This study aimed at understanding this phenomenon from both sociolinguistic and psychological perspectives, viewing language as closely related to power and identity as well as to emotions and close relationships. Qualitative information was gathered from interviews with parents, focusing on parents’ motives to send their children to these educational settings and on the impact of this decision on the family’s language policy and emotional interactions. Overall, findings reveal how the external urban setting interacts with the internal family system. The mixed city context appears to invade the family dynamics in mixed ways, and sociopolitical dimensions interact closely with emotional ones.

Genes for spinocerebellar ataxia with blindness and deafness (SCABD/SCAR3, MIM# 271250 and SCABD2).

Ataxia is a symptom that is often associated with syndromic inherited diseases. We previously reported the linkage of a novel syndrome, ataxia with blindness and deafness (SCAR3/SCABD, OMIM# 271250), to chromosome 6p21-p23 by linkage mapping of an Arab Israeli consanguineous family. We have now identified by whole-exome sequencing a homozygous missense mutation in the Arab Israeli family in the SLC52A2 gene located in 8qter, therefore excluding linkage of this family to 6p. We confirmed the involvement of SLC52A2 by the identification of a second mutation in an independent family with an identical syndromic presentation, which we suggest to name SCABD2. SCABD2 is therefore allelic to Brown-Vialleto-Van Laere syndrome type 2 defined by prominent motoneuronopathy and deafness, and also caused by SLC52A2 mutations. In the course of this project, we identified a clinically similar family with a homozygous missense mutation in PEX6, which is located in 6p21. Therefore, despite false linkage in the initial family, SCABD1/SCAR3 is located in 6p21 and is caused by PEX6 mutations. Both SLC52A2 and PEX6 should be included in screening panels for the diagnosis of syndromic inherited ataxias, particularly as patients with mutations in SLC52A2 can be ameliorated by riboflavin supplementation.

Exome sequencing reveals SYCE1 mutation associated with autosomal recessive primary ovarian insufficiency.

Primary ovarian insufficiency (POI) is caused by ovarian follicle depletion or follicle dysfunction. The phenotypic spectrum ranges from absence of pubertal maturation to early menopause. Genes involved in essential steps in chromosome synapsis and recombination during meiosis, such as synaptonemal complex central element 1 (SYCE1), have been shown to cause POI in animal models. We describe for the first time a homozygous mutation in SYCE1 in humans. To identify the genetic cause of POI in an Israeli Arab family with a consanguineous pedigree. A family-based genetic study conducted at a tertiary medical center. Two daughters of consanguineous parents (first cousins) from a 13-member family were diagnosed with POI. Genotyping was performed in the index patients, their parents, and four unaffected siblings. DNA from the affected sisters was subjected to whole-exome sequencing. The genotypes of interest were confirmed and genotypes of the additional family members were determined by Sanger sequencing. Genotyping was also performed in 90 ethnically matched control individuals. A nonsense homozygous mutation (c.613C>T) was identified in the SYCE1 gene in both affected sisters. The parents and three brothers were heterozygous for the mutation, and an unaffected sister did not carry the mutation. The mutation was not identified in the DNA samples from the 90 control subjects. Given the known function of the SYCE1 gene, we suggest that the nonsense mutation identified accounts for the POI phenotype. These results highlight the importance of the synaptonemal complex and meiosis in ovarian function.