Genetic landscape of recessive diseases in the Vietnamese population from large‐scale clinical exome sequencing

Abstract

Accurate profiling of population‐specific recessive diseases is essential for the design of cost‐effective carrier screening programs. However, minority populations and ethnic groups, including Vietnamese, are still underrepresented in existing genetic studies. Here, we reported the first comprehensive study of recessive diseases in the Vietnamese population. Clinical exome sequencing data of 4503 disease‐associated genes obtained from a cohort of 985 Vietnamese individuals was analyzed to identify pathogenic variants, associated diseases and their carrier frequencies in the population. A total of 118 recessive diseases associated with 164 pathogenic or likely pathogenic variants were identified, among which 28 diseases had carrier frequencies of at least 1% (1 in 100 individuals). Three diseases were prevalent in the Vietnamese population with carrier frequencies of 2–12 times higher than in the world populations, including beta‐thalassemia (1 in 23), citrin deficiency (1 in 31), and phenylketonuria (1 in 40). Seven novel pathogenic and two likely pathogenic variants associated with nine recessive diseases were discovered. The comprehensive profile of recessive diseases identified in this study enables the design of cost‐effective carrier screening programs specific to the Vietnamese population.

Massively parallel sequencing uncovered disease‐associated variant spectra of glucose‐6‐phosphate dehydrogenase deficiency, phenylketonuria and galactosemia in Vietnamese pregnant women

“…Our study showed that 4.6% of Vietnamese pregnant women identified as PAH carriers were asymptomatic at study enrollments. Our study figure was higher than the previously reported PAH frequency of 2.5% (or 1 in 40 individuals) in a cohort of 985 participants from the general population in Vietnam (Tran et al, 2021 ). This earlier publication included 985 participants spanning several age groups (fetuses, neonates, and adults) and both sexes (46% female and 54% male), whilst this study had 3259 pregnant women.…”

“…However, all PAH variants in our study were heterozygous, and this finding is consistent with a previously reported heterozygous predominance (Blau et al, 2014;Hillert et al, 2020;Zschocke et al, 1995). The results from our study reveal that PKU carrier frequency was higher amongst the Vietnamese and other Eastern Asian populations, and it appears that PKU is underreported (Lazarin et al, 2012;Tran et al, 2021).…”

“…It is estimated that 0.45 million people have phenylketonuria worldwide, with a global prevalence of roughly 1 in 24,000 live births (Hillert et al, 2020 ). A recent study showed that PKU is amongst Vietnam's seven most common recessive diseases, with a carrier frequency of 2.5% (Tran et al, 2021 ). The disease frequency of GAL varies from 1 in 23,000 persons in North American and European populations to 1 in 44,000 persons in Asian and African populations (Bosch et al, 2003 ; Lee et al, 2011 ; Ruiz et al, 1999 ; Senemar et al, 2011 ).…”

“…However, these data are limited by geographic variations and ethnic‐specific differences (Hillert et al, 2020 ; Howes et al, 2012 ; Senemar et al, 2011 ). Despite previously reported studies, there is still a lack of large‐scale prenatal genetic screening studies about these three common metabolic diseases amongst Vietnamese and other Asian populations (Lee et al, 2011 ; Matsuo et al, 2003 ; Senemar et al, 2011 ; Tarhani et al, 2021 ; Tran et al, 2021 ). In parallel with the benefits of a newborn genetic screening programme, a prenatal screening programme for pregnant women will bring more benefits in providing carriers with their genetic data.…”