A novel ATRX mutation causes Smith‑Fineman‑Myers syndrome in a Chinese family

Abstract

Smith-Fineman-Myers syndrome (SFMS) is a rare inherited disorder characterized mainly by mental retardation and anomalies in the appearance of patients. SFMS is caused by a mutation in the α-thalassemia/mental retardation syndrome X-linked (ATRX) gene and has an X-linked recessive pattern. in the present study, a novel ATRX mutation was identified, and the association between its genotype and the phenotype was explored in a chinese Han family with SFMS. This study aimed to lay a foundation for prenatal diagnosis for this family. Briefly, genomic DNA was extracted from peripheral blood samples obtained from the family. High-throughput genetic sequencing was employed to detect the whole exome; subsequently, Sanger sequencing was performed to verify the candidate mutations. clinical analysis of the proband was also accomplished. consequently, a novel missense ATRX mutation was identified comprising a single nucleotide change of C to T, which caused an amino acid substitution at codon 172 in exon 7 (c.515c>T; p.Thr172ile) of the proband. This mutation was found to co-segregate in the present SFMS pedigree and was located in a highly conserved region of the aTrX protein, thus suggesting that it may be a pathogenic mutation. Taken together, these findings provided novel information that may lead towards an improved understanding of the genetic and clinical features of patients with SFMS, thereby facilitating a more accurate prenatal diagnosis of SFMS.

Identification of a Hemizygous Novel Splicing Variant in ATRX Gene: A Case Report and Literature Review

“…Overall, in this case, in addition to the above symptoms, there are obvious feeding difficulties and gastrointestinal symptoms. These symptoms have been reported in other cases ( 17 , 38 ). Furuta et al found that gastrointestinal disorders were closely related to intellectual disability, cerebral palsy, epilepsy, and other neurodevelopmental disorders.…”

A novel exomal ATRX mutation with preferential transmission to offspring: A case report and review of the literature for transmission ratio distortion in ATRX families

“…To investigate the possibility that mutant ATRX alleles were preferentially transmitted to offspring, a meta-analysis of published pedigrees with complete reporting of family structures was conducted. data on transmission of ATRX alleles for 42 mothers were extracted from papers published between 1991 and 2019 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Probands and index cases were excluded from the calculations, as well as offspring from one mosaic mother.…”

“…The chi-square test applied to our sample was P=0.29, which does not reach statistical significance. next, the analysis was limited to a subset of families where the mutations were identified, and all members of the family were genotyped (Table II) (8)(9)(10)(11)(12)(14)(15)(16)(17). A modest sex-ratio distortion was observed in favor of the male offspring, as well as transmission-ratio distortion in favor of the ATRX mutant alleles, but these did not reach statistical significance either (Table II).…”