Clinical and genetic analysis of a child with X-linked intellectual developmental disorder due to a novel variant of NEXMIF gene

Abstract

To explore the genetic basis for a child featuring facial dysmorphism and intellectual disabilities. A child who was diagnosed at Linyi People's Hospital on January 5 2023 due to "mental retardation" was selected as the study subject. Peripheral blood samples of the child and his parents, in addition with an amniotic fluid sample from the his mother were collected for the extraction of genomic DNA. Whole exome sequencing was carried out for the child, and candidate variant was verified by Sanger sequencing of his family members. The child was found to harbor a hemizygous c.1123dupG (p.E375Gfs*4) variant of the NEXMIF gene, for which both of his parents and the fetus were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+PS2-P+PM2-P). A healthy infant was subsequently born. The hemizygous c.1123dupG (p.E375Gfs*4) variant of the NEXMIF gene probably underlay the disease in this child. Based on his clinical phenotype and genotype, the child was ultimately diagnosed with X-linked intellectual developmental disorder-98. Above finding has also enriched the mutational spectrum of the NEXMIF gene.