[Genetic analysis of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 due to variant of PIGN gene].

OBJECTIVE

To analyze the clinical phenotype and genetic etiology of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1).

METHODS

Clinical data of a 2-year-old boy who had presented at the Affiliated Hospital of Qingdao University in March 2023 for "intermittent limb twitching for 2 years" was collected. Peripheral blood samples were collected from the child and his parents for whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).

RESULTS

The child had manifested with distinctive facial features, limb deformities, hypotonia, motor and intellectual delays, and epileptic seizures. WES revealed that he has harbored compound heterozygous variants of the PIGN gene, namely c.963G>A (p.Q321=) and c.994A>T (p.I332F), which were inherited from his phenotypically normal mother and father, respectively. Based on the ACMG guidelines, the c.963G>A was classified as a pathogenic variant (PVS1+PM2_Supporting+PM3), whilst the c.994A>T was classified as a variant of uncertain significance (PM2_Supporting+PP3).

CONCLUSION

Above discovery has expanded the mutational spectrum of the PIGN gene variants associated with MCAHS1, which may facilitate delineation of its genotype-phenotype correlation.