Carrier frequency and incidence estimation of familial hemophagocytic lymphohistiocytosis in East Asian populations by genome aggregation database (gnomAD) based analysis
ObjectivesHemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome characterized by a life-threatening condition caused by severe hypercytokinemia. The hereditary forms of HLH, also called familial HLH (fHLH), have 4 different genes (PRF1, UNC13D, STX11, and STXBP2) and have been identified a...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2022.975665/full |
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| author | Jong Eun Park Taeheon Lee Kyeongsu Ha Eun Hye Cho Chang-Seok Ki |
| author_facet | Jong Eun Park Taeheon Lee Kyeongsu Ha Eun Hye Cho Chang-Seok Ki |
| author_sort | Jong Eun Park |
| collection | DOAJ |
| description | ObjectivesHemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome characterized by a life-threatening condition caused by severe hypercytokinemia. The hereditary forms of HLH, also called familial HLH (fHLH), have 4 different genes (PRF1, UNC13D, STX11, and STXBP2) and have been identified as being causative for fHLH. This study aimed to analyze the carrier frequency and expected incidence of fHLH in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD).MethodsWe analyzed 9,197 exomes for East Asian populations from gnomAD with 1,909 Korean for four fHLH genes. All identified variants were classified according to 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline.Results19 pathogenic variant/likely pathogenic variants (PV/LPVs) were identified in 30 East Asian individuals (0.33%). Among them, 7 PV/LPVs were identified in 17 Korean individuals (0.63%). The estimated incidence of fHLH was 1 in 1,105,652 for East Asians and l in 235,128 for Koreans.ConclusionsThis study is the first to identify carrier frequencies in East Asian and Korean populations for fHLH using gnomAD. It was confirmed that the carrier frequency of fHLH patients was high in Koreans among East Asians and the incidence was also predicted to be higher than that of other East Asians. The variant spectrum of fHLH genes in East Asian and Korean populations differed greatly from those of other ethnic groups. |
| first_indexed | 2024-04-11T06:59:05Z |
| format | Article |
| id | doaj.art-9a750a0cb3e44d99a1f7e8655af63503 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-04-11T06:59:05Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-9a750a0cb3e44d99a1f7e8655af635032022-12-22T04:38:52ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602022-11-011010.3389/fped.2022.975665975665Carrier frequency and incidence estimation of familial hemophagocytic lymphohistiocytosis in East Asian populations by genome aggregation database (gnomAD) based analysisJong Eun Park0Taeheon Lee1Kyeongsu Ha2Eun Hye Cho3Chang-Seok Ki4Department of Laboratory Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, South KoreaGC Genome, Yongin, South KoreaGC Genome, Yongin, South KoreaDepartment of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South KoreaGC Genome, Yongin, South KoreaObjectivesHemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome characterized by a life-threatening condition caused by severe hypercytokinemia. The hereditary forms of HLH, also called familial HLH (fHLH), have 4 different genes (PRF1, UNC13D, STX11, and STXBP2) and have been identified as being causative for fHLH. This study aimed to analyze the carrier frequency and expected incidence of fHLH in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD).MethodsWe analyzed 9,197 exomes for East Asian populations from gnomAD with 1,909 Korean for four fHLH genes. All identified variants were classified according to 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline.Results19 pathogenic variant/likely pathogenic variants (PV/LPVs) were identified in 30 East Asian individuals (0.33%). Among them, 7 PV/LPVs were identified in 17 Korean individuals (0.63%). The estimated incidence of fHLH was 1 in 1,105,652 for East Asians and l in 235,128 for Koreans.ConclusionsThis study is the first to identify carrier frequencies in East Asian and Korean populations for fHLH using gnomAD. It was confirmed that the carrier frequency of fHLH patients was high in Koreans among East Asians and the incidence was also predicted to be higher than that of other East Asians. The variant spectrum of fHLH genes in East Asian and Korean populations differed greatly from those of other ethnic groups.https://www.frontiersin.org/articles/10.3389/fped.2022.975665/fullfamilial hemophagocytic lymphohistiocytosisgnomADcarrier frequencyEast AsianKorean |
| spellingShingle | Jong Eun Park Taeheon Lee Kyeongsu Ha Eun Hye Cho Chang-Seok Ki Carrier frequency and incidence estimation of familial hemophagocytic lymphohistiocytosis in East Asian populations by genome aggregation database (gnomAD) based analysis Frontiers in Pediatrics familial hemophagocytic lymphohistiocytosis gnomAD carrier frequency East Asian Korean |
| title | Carrier frequency and incidence estimation of familial hemophagocytic lymphohistiocytosis in East Asian populations by genome aggregation database (gnomAD) based analysis |
| title_full | Carrier frequency and incidence estimation of familial hemophagocytic lymphohistiocytosis in East Asian populations by genome aggregation database (gnomAD) based analysis |
| title_fullStr | Carrier frequency and incidence estimation of familial hemophagocytic lymphohistiocytosis in East Asian populations by genome aggregation database (gnomAD) based analysis |
| title_full_unstemmed | Carrier frequency and incidence estimation of familial hemophagocytic lymphohistiocytosis in East Asian populations by genome aggregation database (gnomAD) based analysis |
| title_short | Carrier frequency and incidence estimation of familial hemophagocytic lymphohistiocytosis in East Asian populations by genome aggregation database (gnomAD) based analysis |
| title_sort | carrier frequency and incidence estimation of familial hemophagocytic lymphohistiocytosis in east asian populations by genome aggregation database gnomad based analysis |
| topic | familial hemophagocytic lymphohistiocytosis gnomAD carrier frequency East Asian Korean |
| url | https://www.frontiersin.org/articles/10.3389/fped.2022.975665/full |
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