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.

The X-linked alpha-thalassemia mental retardation (ATR-X) syndrome is a rare genetic condition caused by mutations in the X-encoded gene ATRX. Here we describe two unrelated patients of Sri Lankan origin with novel missense variants in the ATRX gene: c.839C>T|p.Cys280Tyr and c.5369C>T|p.Ala1790Val. These two novel variants were associated with variable phenotypes which clinically resembled X-linked mental retardation-hypotonic facies syndrome and Smith-Fineman-Myers syndrome respectively. These cases expand the clinical spectrum of ATR-X syndrome and open new opportunities for the molecular diagnosis of ATRX mutations in male patients with severe global developmental delay and intellectual disabilities.