[Prenatal diagnosis and genetics analysis of a fetus with type 27 intellectual disability syndrome due to variant of SRRM2 gene].

OBJECTIVE

To explore the clinical phenotype and genetic etiology of a fetus with autosomal dominant intellectual disability type 72 (MRD72) resulting from a variant of the SRRM2 gene.

METHODS

A Chinese pedigree with MRD72 (fetus) who had visited the Affiliated Women and Children's Hospital of Ningbo University in November 2024 was selected as study subject. Clinical data of the pedigree were collected. Amniotic fluid and peripheral blood samples were collected from the fetus and its parents for genomic DNA extraction. Whole-exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing of the family members and rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature on MRD72 were searched in domestic and international databases for a review. This study was approved by the hospital (Ethics No.: EC2023-094).

RESULTS

The proband was a fetus of 25 weeks of gestation. Fetal echocardiography revealed a relatively small left atrium and left ventricle, along with a diminished aortic-to-pulmonary artery ratio. WES revealed that the fetus has harbored a heterozygous nonsense variant of the SRRM2 gene. Sanger sequencing confirmed both parents carried the wild-type alleles. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PVS1+PM2_Supporting) and has not been recorded in public databases. Bioinformatic analysis predicted amino acid 512 to be highly conserved across various species. According to the pre-set literature search strategy, 4 publications were retrieved, which involved 30 MRD72 patients from 27 pedigrees, In addition to this study, a total of 31 cases were included. Analysis of clinical features and genetic etiology showed that patients with MRD72 presented mainly with clinical manifestations such as mental and motor development delay, special facial features, speech/intellectual development delay, and obesity. The genetic etiology was all variants at relevant loci of the SRRM2 gene.

CONCLUSION

The SRRM2 variant identified in this study is implicated as the genetic cause of MRD72 in the proband. Above results have expanded the mutational and phenotypic spectra of the SRRM2 gene.