Carrier frequency estimation of pathogenic variants of autosomal recessive and X-linked recessive Mendelian disorders using exome sequencing data in 1,642 Thais

Abstract

AbstractPeople with autosomal recessive disorders often were born without awareness of the carrier status of their parents. The American College of Medical Genetics and Genomics (ACMG) recommends screening 113 genes known to cause autosomal recessive and X-linked conditions in couples seeking to learn about their risk of having children with these disorders to have an appropriate reproductive plan. Here, we analyzed the exome sequencing data of 1,642 unrelated Thai individuals to identify the pathogenic variant (PV) frequencies in genes recommended by ACMG. The ascertainment bias was controlled by excluding the carriers of the PV in the genes for the conditions that are attributed to their offspring disorders. In the 113 ACMG-recommended genes, 165 PV and likely PVs in 60 genes of 559 exomes (34%, 559/1642) were identified. The carrier rate was increased to 39% when glucose-6-phosphate dehydrogenase (G6PD) was added. The carrier rate was still as high as 14.7% when thalassemia and hemoglobinopathies were excluded. In addition to thalassemia, hemoglobinopathies, and G6PD deficiency, carrier frequencies of >1% were found for Gaucher disease, primary hyperoxaluria, Pendred syndrome, and Wilson disease. Nearly 2% of the couples were at risk of having offsprings with the tested autosomal recessive conditions. The expanded carrier screening focused on common autosomal recessive conditions in Thai seems to be benefit among the study samples.