1ｐ36欠失症候群

BACKGROUND: The 1p36 deletion syndrome is a subtelomeric deletion syndrome characterized by developmental delay, epilepsy, and distinctive facial features. The diagnostic rate has improved with advances in genetic testing, including chromosomal microarray analysis. However, little is known about the psychosocial impact of a child's diagnosis on parents. This study aimed to explore the psychosocial experiences related to parenting among parents of children with 1p36 deletion syndrome. METHODS: The questionnaire survey was conducted among parents of children with 1p36 deletion syndrome, through the Japanese family association related to the syndrome. The questionnaire included items on the characteristics of parents and their children, information sources for 1p36 deletion syndrome, and complications and issues related to this syndrome. Parental mental health was assessed using measures of psychological distress and subjective well-being, with affiliate stigma examined as a key factor associated with mental health outcomes, along with other psychological variables including parental strain and self-esteem. RESULTS: Thirty-nine parents (mean age: 43.1 years) responded to the questionnaire. The mean age of the child at diagnosis was 1.9 years. Most parents obtained information from the internet, and information from medical and genetic specialists was limited. Parental challenges in medical and welfare aspects were diverse and varied by the child's developmental stage. Exploratory path analysis suggested that the association between affiliate stigma and mental health may be mediated by parental strain and self-esteem. Furthermore, affiliate stigma was significantly higher in parents of children with 1p36 deletion syndrome than in those with Down syndrome. CONCLUSIONS: Parents of children with 1p36 deletion syndrome experience limited access to information from medical and genetic specialists, diverse medical and welfare challenges across developmental stages, and potentially high levels of affiliate stigma. These findings suggest the need for psychosocial support that considers the potential impact of affiliate stigma and is tailored to the evolving challenges experienced across the child's developmental stages.

Haploinsufficiency of SKI, PRDM16, RERE, PAX7, and GRHL3 have been implicated in the development of orofacial clefting (OFC) associated with chromosome 1p36 deletions based on human and/or mouse data. Haploinsufficiency of SPEN, a 1p36 gene that encodes a transcriptional repressor, causes Radio-Tartaglia syndrome, a neurodevelopmental syndrome in which high/narrow palates are common, and OFC is occasionally observed. We show that Spen-null embryos have abnormal palatal shelf elevation and extension leading to the development of cleft palate. Mesenchymal cell proliferation in the medial halves of the palatal shelves of Spen-null embryos at E13.5 is significantly reduced. This contributes to the delay of palatal shelf elevation. Tissue specific ablation of Spen in the cranial neural crest cells results in delayed palatal development. This pattern of abnormal palatal development mimics the pattern described in RERE-deficient mice. We show that Rere and Spen are expressed in same cell types, that Rere and Spen interact genetically in the development of the palate, that Spen expression is reduced in the palates of RERE-deficient embryos at E14.5, and that the rate of OFC in individuals with 1p36 deletions involving both RERE and SPEN is higher than those of individuals with RERE or SPEN haploinsufficiency. Our results suggest that SPEN is required for normal mammalian palatal development, that RERE and SPEN interact in a common pathway during palatal development, and that haploinsufficiency of RERE and SPEN are likely to contribute to the development of OFC in individuals with 1p36 deletions.

The most prevalent terminal chromosomal deletion disorder, chromosome 1p36 deletion syndrome, leads to developmental delays and intellectual disabilities and seizures and heart defects and distinct facial appearance. Traditional cytogenetic methods, which include karyotyping, face difficulties in early detection of these abnormalities because it require extensive work and substantial time and it can only identify major genetic changes, which makes it unsuitable for detecting minor genomic alterations that occur during infancy. The field of Deep Learning (DL) has made progress toward improving genomic data analysis and disease-related gene identification since its introduction. Hence, the MultiSight Transformer functions as a proposed framework, which processes gene sequences through its multi-head self-attention mechanism to study 1p36 chromosome 1 deletion effects. The model used training and testing procedures on combined datasets which included genomic variations from chromosome 1 and 1p36 deletion regions that contained copy number variations linked to clinical symptoms of skeletal and gastrointestinal and cardiac and chronic kidney disease. The proposed method enables effective gene sequence classification and prediction of the contribution of 1p36 deletion syndrome to major clinical conditions. The experimental results show that the model reaches an accuracy of 0.97 and a precision of 0.90 and a recall of 0.9195 and an F1-score of 0.90 and an area under the curve (AUC) of 0.94 which demonstrates its strong predictive performance. The findings demonstrate that researchers can enhance the detection accuracy and efficiency of chromosome 1p36 deletion syndrome through the combination of transformer-based deep learning models with genomic data analysis. The findings 1p36 deletion detection research should support early diagnosis and clinical decision-making activities.

STUDY OBJECTIVE: We reported a rare case of 1p36 deletion syndrome diagnosed using whole-exome sequencing (WES) in a Tunisian neonate, and to highlight the utility of WES in detecting structural variants, particularly in resource-limited settings. METHODS: Clinical and genetic investigations were conducted on a female neonate presenting with a severe polymalformative syndrome. WES was performed to detect potential genetic abnormalities, followed by validation through fluorescence in situ hybridization (FISH). Variant annotation and classification were done in accordance with ACMG guidelines. RESULTS: WES identified a heterozygous interstitial deletion in the 1p36 region, spanning 11.64 Mb and affecting 155 coding genes, including key genes such as MMP23B, GABRD, SKI, PRDM16, KCNAB2, RERE, UBE4B, and CASZ1. The deletion was classified as pathogenic, and FISH analysis confirmed its presence. Clinically, the patient exhibited intrauterine growth restriction, neonatal epilepsy, craniofacial dysmorphia, congenital heart defect, and agenesis of the corpus callosum. CONCLUSION: This is the first reported case in Tunisia of a 1p36 deletion identified via short-read WES. The findings support the expanding role of WES in structural variant detection and underscore its diagnostic value, especially in settings with limited access to chromosomal microarray or genome sequencing technologies.