Analysis of TWNK variant in a family affected with Perrault syndrome / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To explore the genetic etiology of two patients with Perrault syndrome (PRLTS) in a family.@*METHODS@#Whole exome sequencing (WES) was carried out to screen potential variants within genomic DNA extracted from the proband. Suspected variants were validated by clinical data and results of Sanger sequencing.@*RESULTS@#WES has identified two heterozygous variants of TWNK gene, namely c.1172G>A (p.Arg391His) and c.1844G>C (p.Gly615Ala). Sanger sequencing confirmed that the c.1172G>A (p.Arg391His), a known pathogenic variant, was derived from her father, while the c.1844G>C (p.Gly615Ala), a novel variant, was derived from her mother. Her brother, who was similarly affected, has carried the same compound heterozygous variants.@*CONCLUSION@#The compound heterozygous variants c.1172G>A (p.Arg391His) and c.1844G>C (p.Gly615Ala) of the TWNK gene probably underlie PRLTS in the sib pair. The above results have facilitated genetic counseling and prenatal diagnosis for the affected family.