{"title":"HYAL2中新型复合杂合变异体引起的透明质酸酶2缺陷:临床严重程度不同的兄弟姐妹HYAL2缺陷病例报告及文献复习","authors":"Ryuta Orimoto, Eriko Adachi, Maki Gau, Yoko Saito, Haruki Yamano, Hisae Nakatani, Shizuka Kirino, Kengo Moriyama, Yohei Yamaguchi, Tomoko Mizuno, Taku Ishii, Masayuki Yoshida, Kenichi Kashimada, Kei Takasawa","doi":"10.1038/s10038-025-01333-1","DOIUrl":null,"url":null,"abstract":"<p><p>This study reports the first Asian case of syndromic cleft lip and palate resembling CHARGE-like syndrome, caused by novel compound heterozygous variants of the HYAL2 gene. Hyaluronidase-2 (HYAL2) plays a critical role in hyaluronic acid degradation and tissue remodelling. A 2-year-old Japanese boy presented with growth deficiency, congenital heart disease, craniofacial dysmorphism, micropenis, and developmental delays-features that overlapped with those of CHARGE syndrome. Genetic analysis identified two rare HYAL2 missense variants (c.1133G>A, p.Arg378His; c.1271A>G, p.His424Arg), classified as \"likely pathogenic\" based on ACMG/AMP criteria. This case highlights the importance of considering HYAL2 deficiency in the syndromic presentation of cleft lip and palate with congenital heart disease, particularly in the absence of CHD7 abnormalities. This study also emphasizes potential primary testicular dysfunction in male patients with HYAL2 deficiency and underscores the need for further research to clarify genotype-phenotype correlations and pathology.</p>","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":"321-324"},"PeriodicalIF":2.6000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hyaluronidase 2 deficiency due to novel compound heterozygous variants in HYAL2: a case report of siblings with HYAL2 deficiency showing different clinical severity and literature review.\",\"authors\":\"Ryuta Orimoto, Eriko Adachi, Maki Gau, Yoko Saito, Haruki Yamano, Hisae Nakatani, Shizuka Kirino, Kengo Moriyama, Yohei Yamaguchi, Tomoko Mizuno, Taku Ishii, Masayuki Yoshida, Kenichi Kashimada, Kei Takasawa\",\"doi\":\"10.1038/s10038-025-01333-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This study reports the first Asian case of syndromic cleft lip and palate resembling CHARGE-like syndrome, caused by novel compound heterozygous variants of the HYAL2 gene. Hyaluronidase-2 (HYAL2) plays a critical role in hyaluronic acid degradation and tissue remodelling. A 2-year-old Japanese boy presented with growth deficiency, congenital heart disease, craniofacial dysmorphism, micropenis, and developmental delays-features that overlapped with those of CHARGE syndrome. Genetic analysis identified two rare HYAL2 missense variants (c.1133G>A, p.Arg378His; c.1271A>G, p.His424Arg), classified as \\\"likely pathogenic\\\" based on ACMG/AMP criteria. This case highlights the importance of considering HYAL2 deficiency in the syndromic presentation of cleft lip and palate with congenital heart disease, particularly in the absence of CHD7 abnormalities. This study also emphasizes potential primary testicular dysfunction in male patients with HYAL2 deficiency and underscores the need for further research to clarify genotype-phenotype correlations and pathology.</p>\",\"PeriodicalId\":16077,\"journal\":{\"name\":\"Journal of Human Genetics\",\"volume\":\" \",\"pages\":\"321-324\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Human Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1038/s10038-025-01333-1\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/3/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Human Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s10038-025-01333-1","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/31 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Hyaluronidase 2 deficiency due to novel compound heterozygous variants in HYAL2: a case report of siblings with HYAL2 deficiency showing different clinical severity and literature review.
This study reports the first Asian case of syndromic cleft lip and palate resembling CHARGE-like syndrome, caused by novel compound heterozygous variants of the HYAL2 gene. Hyaluronidase-2 (HYAL2) plays a critical role in hyaluronic acid degradation and tissue remodelling. A 2-year-old Japanese boy presented with growth deficiency, congenital heart disease, craniofacial dysmorphism, micropenis, and developmental delays-features that overlapped with those of CHARGE syndrome. Genetic analysis identified two rare HYAL2 missense variants (c.1133G>A, p.Arg378His; c.1271A>G, p.His424Arg), classified as "likely pathogenic" based on ACMG/AMP criteria. This case highlights the importance of considering HYAL2 deficiency in the syndromic presentation of cleft lip and palate with congenital heart disease, particularly in the absence of CHD7 abnormalities. This study also emphasizes potential primary testicular dysfunction in male patients with HYAL2 deficiency and underscores the need for further research to clarify genotype-phenotype correlations and pathology.
期刊介绍:
The Journal of Human Genetics is an international journal publishing articles on human genetics, including medical genetics and human genome analysis. It covers all aspects of human genetics, including molecular genetics, clinical genetics, behavioral genetics, immunogenetics, pharmacogenomics, population genetics, functional genomics, epigenetics, genetic counseling and gene therapy.
Articles on the following areas are especially welcome: genetic factors of monogenic and complex disorders, genome-wide association studies, genetic epidemiology, cancer genetics, personal genomics, genotype-phenotype relationships and genome diversity.