This preprint is under consideration at Orphanet Journal of Rare Diseases. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Research
Chang-Seok Ki
GC Genome
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7679-8731
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
Smith–Lemli–Opitz syndrome, DHCR7, gnomAD, carrier frequency, East Asian
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CURRENT STATUS: Under Review
Version 1
Posted 19 Jan, 2021
No community comments so far
Editorial decision: Minor revision
On 23 Feb, 2021
Review #2 received
Received 21 Feb, 2021
Review #1 received
Received 17 Feb, 2021
Reviewer #2 agreed
On 08 Feb, 2021
Reviewers invited
Invitations sent on 30 Jan, 2021
Reviewer #1 agreed
On 30 Jan, 2021
Editor assigned
On 16 Jan, 2021
Submission checks complete
On 16 Jan, 2021
Editor invited
On 16 Jan, 2021
First submitted
On 07 Jan, 2021
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Subject Areas
Internal Medicine
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This preprint is under consideration at Orphanet Journal of Rare Diseases. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Chang-Seok Ki
GC Genome
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7679-8731
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 19 Jan, 2021
No community comments so far
Editorial decision: Minor revision
On 23 Feb, 2021
Review #2 received
Received 21 Feb, 2021
Review #1 received
Received 17 Feb, 2021
Reviewer #2 agreed
On 08 Feb, 2021
Reviewers invited
Invitations sent on 30 Jan, 2021
Reviewer #1 agreed
On 30 Jan, 2021
Editor assigned
On 16 Jan, 2021
Submission checks complete
On 16 Jan, 2021
Editor invited
On 16 Jan, 2021
First submitted
On 07 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
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