Intellectual disorder type 98 caused by a novel NEXMIF variant: a case report and literature review

Background: Intellectual disorder, Type 98 (ID 98) is an X-linked disorder characterized by intellectual disability, epilepsy, and multisystem manifestations. This condition is caused by pathogenic variants in the NEXMIF gene through X-linked dominant inheritance. Case presentation: We identified a novel hemizygous NEXMIF variant (c.1939_1942delinsAT, p.S647Ifs*3) in a 5-year-old male with severe intellectual disability via trio whole-exome sequencing. His mildly affected mother was a heterozygous carrier. Prenatal diagnosis for the mother's subsequent pregnancy identified the same hemizygous variant in the male fetus. Following genetic counseling, the decision was made to terminate the pregnancy, thereby preventing the clinical manifestation of the disease in the offspring. Conclusion: This report expands the NEXMIF mutational spectrum and underscores the critical role of genetic testing in achieving early diagnosis and informed reproductive counseling for families affected by this disorder.