A novel nonsense variant in the CHD7 gene in a patient with CHARGE syndrome in Yakutia

CHARGE syndrome is a rare autosomal dominant disease caused by mutational lesions in the CHD7 and SEMA3E genes (OMIM 214800). The prevalence is approximately 1 in 12,000 newborns. Most cases of CHARGE syndrome are caused by de novo pathogenic variants of the CHD7 gene, which encodes the DNA-binding protein helicase 7 chromodomain, which is responsible for chromatin organization. The abbreviation “CHARGE” summarizes six clinical signs of the syndrome: C - coloboma, H - heart defects, A - atresia of choanae, R - retardation of growth and/or development, G - genital anomalies, E - ear abnormalities. This paper presents a genotype-phenotypic analysis of a case with a previously unknown nonsense substitution c.1940C>G (p.Ser647*) in the CHD7 gene, identified by whole exome sequencing in a patient with an initially undifferentiated form of hearing loss associated with multiple developmental anomalies. As a result of a clinical examination, the patient revealed 7 signs that correspond to the updated diagnostic criteria for CHARGE syndrome: three main ones (anomalies of the inner ear, ocular coloboma and pathogenic variant in the CHD7 gene) and four secondary signs (mental retardation, congenital heart disease, cranial nerve dysfunction, hypothalamic-pituitary dysfunction). The paper discusses the relationship with this syndrome of the identified two additional signs from the endocrine system and the musculoskeletal system, not included in the latest version of the diagnostic criteria for the CHARGE syndrome. We hope that close attention to genotype-phenotypic characteristics will help determine how best to diagnose, counsel and provide the necessary medical and social care for patients with such rare diseases.

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