RESUMO
BACKGROUND: High resolution genome-wide copy number analysis, routinely used in clinical diagnosis for several years, retrieves new and extremely rare copy number variations (CNVs) that provide novel candidate genes contributing to disease etiology. The aim of this work was to identify novel genetic causes of neurodevelopmental disease, inferred from CNVs detected by array comparative hybridization (aCGH), in a cohort of 325 Portuguese patients with intellectual disability (ID). RESULTS: We have detected CNVs in 30.1% of the patients, of which 5.2% corresponded to novel likely pathogenic CNVs. For these 11 rare CNVs (which encompass novel ID candidate genes), we identified those most likely to be relevant, and established genotype-phenotype correlations based on detailed clinical assessment. In the case of duplications, we performed expression analysis to assess the impact of the rearrangement. Interestingly, these novel candidate genes belong to known ID-related pathways. Within the 8% of patients with CNVs in known pathogenic loci, the majority had a clinical presentation fitting the phenotype(s) described in the literature, with a few interesting exceptions that are discussed. CONCLUSIONS: Identification of such rare CNVs (some of which reported for the first time in ID patients/families) contributes to our understanding of the etiology of ID and for the ever-improving diagnosis of this group of patients.
Assuntos
Deficiência Intelectual/genética , Aberrações Cromossômicas , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA/genética , Feminino , Estudos de Associação Genética , Genômica , Histona-Lisina N-Metiltransferase/genética , Humanos , Masculino , Linhagem , FenótipoRESUMO
We present the extremely rare case of a male newborn with Beckwith-Wiedemann Syndrome (BWS) presenting as delayed abdominal wall closure and neonatal intussusception. Fetal ultrasound had shown omphalocele that resolved spontaneously. When feeding was attempted, he had various episodes of vomiting. An x-ray showed signs of high bowel obstruction. Jejunal intussusception was found on laparotomy. Enterectomy and primary jejuno-jejunal anastomosis was performed. During post-operative period subtle physical findings became prominent: plain hemangioma, posterior helical indentations, and macroglossia. Cardiac ultrasonography showed a patent foramen oval with small left-to-right shunt. Ultrasonography showed renal hyperplasia. Genetic study showed hypomethylation of DMR2 region of 11p15 chromosome.
