Carrier Frequency and Incidence Estimation of Smith–Lemli–Opitz syndrome in East Asian Populations by Genome Aggregation Database (gnomAD) Based Analysis
Background: Smith–Lemli–Opitz syndrome (SLOS) is an autosomal, recessively inherited congenital malformation syndrome characterized by multiple congenital anomalies such as microcephaly with mental defects, distinctive facial features, genital abnormalities, and 2-3 syndactyly of the toes. SLOS is caused by defective 7-dehydrocholesterol reductase, which is encoded by the DHCR7 gene. This study aimed to analyze the carrier frequency and expected incidence of SLOS in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD) through the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline (2015 ACMG-AMP guideline).
Methods: We analyzed 9,197 exomes for East Asian populations from gnomAD, comprising 1,909 Korean, 76 Japanese, and 7,212 other East Asian populations. All identified variants were classified according to 2015 ACMG-AMP guideline.
Results: According to the 2015 ACMG-AMP guideline, 15 pathogenic variant/likely pathogenic variant (PV/LPV) cases were identified in 33 East Asian individuals (39/9,191 = 0.4%). Among them, four PVs/LPVs were identified in 19 Korean individuals (19/1,909 = 1.0%). The estimated incidence of SLOS is 1 in 310,688 in East Asians and l in 40,380 in Koreans.
Conclusions: This study is the first to identify carrier frequencies in East Asians and Koreans using gnomAD. It was confirmed that East Asians had a lower carrier frequency than did other ethnicities, and Koreans had lower or similar carrier frequencies. The variant spectrums of DHCR7 in East Asian and Korean populations differed greatly from those of other ethnic groups.
Posted 19 Jan, 2021
Received 21 Feb, 2021
Received 17 Feb, 2021
On 08 Feb, 2021
Invitations sent on 30 Jan, 2021
On 30 Jan, 2021
On 16 Jan, 2021
On 16 Jan, 2021
On 16 Jan, 2021
On 07 Jan, 2021
Carrier Frequency and Incidence Estimation of Smith–Lemli–Opitz syndrome in East Asian Populations by Genome Aggregation Database (gnomAD) Based Analysis
Posted 19 Jan, 2021
Received 21 Feb, 2021
Received 17 Feb, 2021
On 08 Feb, 2021
Invitations sent on 30 Jan, 2021
On 30 Jan, 2021
On 16 Jan, 2021
On 16 Jan, 2021
On 16 Jan, 2021
On 07 Jan, 2021
Background: Smith–Lemli–Opitz syndrome (SLOS) is an autosomal, recessively inherited congenital malformation syndrome characterized by multiple congenital anomalies such as microcephaly with mental defects, distinctive facial features, genital abnormalities, and 2-3 syndactyly of the toes. SLOS is caused by defective 7-dehydrocholesterol reductase, which is encoded by the DHCR7 gene. This study aimed to analyze the carrier frequency and expected incidence of SLOS in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD) through the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline (2015 ACMG-AMP guideline).
Methods: We analyzed 9,197 exomes for East Asian populations from gnomAD, comprising 1,909 Korean, 76 Japanese, and 7,212 other East Asian populations. All identified variants were classified according to 2015 ACMG-AMP guideline.
Results: According to the 2015 ACMG-AMP guideline, 15 pathogenic variant/likely pathogenic variant (PV/LPV) cases were identified in 33 East Asian individuals (39/9,191 = 0.4%). Among them, four PVs/LPVs were identified in 19 Korean individuals (19/1,909 = 1.0%). The estimated incidence of SLOS is 1 in 310,688 in East Asians and l in 40,380 in Koreans.
Conclusions: This study is the first to identify carrier frequencies in East Asians and Koreans using gnomAD. It was confirmed that East Asians had a lower carrier frequency than did other ethnicities, and Koreans had lower or similar carrier frequencies. The variant spectrums of DHCR7 in East Asian and Korean populations differed greatly from those of other ethnic groups.