{"title":"在一个中国家族中鉴定并体内功能分析导致甲状旁腺功能减退症、感音神经性耳聋和肾发育不良综合征的新型 GATA3 错义突变。","authors":"Shuyao Pan, Shushu Long, Liangchun Cai, Junping Wen, Wei Lin, Gang Chen","doi":"10.1007/s12020-024-04087-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant genetic disease associated with mutations in the GATA3 gene, which encodes GATA3 that plays essential roles in vertebrate development. This study aimed to identify and report the pathogenic mutation in GATA3 in a Chinese family diagnosed with HDR syndrome and determine its functional impacts in vivo.</p><p><strong>Subjects and methods: </strong>The clinical features of a 25-year-old male patient with HDR syndrome and his parents were collected. GATA3 gene exome sequencing and Sanger sequencing were performed on the proband and his family, respectively. Functional analyses of GATA3 were performed using bioinformatics tools and zebrafish assays to determine pathogenicity and phenotype spectrum.</p><p><strong>Results: </strong>A novel, heterozygous, missense mutation in exon 4 of the GATA3 gene, c.863 G > A, p.Cys288Tyr, in the proband and his mother who presented the complete HDR triad, was predicted to be deleterious by in silico tools. 3D structure modeling showed that the variant caused significant structural changes. In vivo studies using a zebrafish animal model revealed the deleterious impact of the variant on the gill buds, otoliths, and pronephros.</p><p><strong>Conclusion: </strong>We identified a novel missense mutation, GATA3 p.Cys288Tyr, within a family with HDR syndrome and delineated it as a loss-of-function variant in vivo. This expands the spectrum of GATA3 mutations associated with HDR syndrome in the Chinese population and mimics HDR-related changes in vivo.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification and in vivo functional analysis of a novel missense mutation in GATA3 causing hypoparathyroidism, sensorineural deafness and renal dysplasia syndrome in a Chinese family.\",\"authors\":\"Shuyao Pan, Shushu Long, Liangchun Cai, Junping Wen, Wei Lin, Gang Chen\",\"doi\":\"10.1007/s12020-024-04087-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant genetic disease associated with mutations in the GATA3 gene, which encodes GATA3 that plays essential roles in vertebrate development. This study aimed to identify and report the pathogenic mutation in GATA3 in a Chinese family diagnosed with HDR syndrome and determine its functional impacts in vivo.</p><p><strong>Subjects and methods: </strong>The clinical features of a 25-year-old male patient with HDR syndrome and his parents were collected. GATA3 gene exome sequencing and Sanger sequencing were performed on the proband and his family, respectively. Functional analyses of GATA3 were performed using bioinformatics tools and zebrafish assays to determine pathogenicity and phenotype spectrum.</p><p><strong>Results: </strong>A novel, heterozygous, missense mutation in exon 4 of the GATA3 gene, c.863 G > A, p.Cys288Tyr, in the proband and his mother who presented the complete HDR triad, was predicted to be deleterious by in silico tools. 3D structure modeling showed that the variant caused significant structural changes. In vivo studies using a zebrafish animal model revealed the deleterious impact of the variant on the gill buds, otoliths, and pronephros.</p><p><strong>Conclusion: </strong>We identified a novel missense mutation, GATA3 p.Cys288Tyr, within a family with HDR syndrome and delineated it as a loss-of-function variant in vivo. This expands the spectrum of GATA3 mutations associated with HDR syndrome in the Chinese population and mimics HDR-related changes in vivo.</p>\",\"PeriodicalId\":49211,\"journal\":{\"name\":\"Endocrine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-11-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Endocrine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12020-024-04087-6\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12020-024-04087-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Identification and in vivo functional analysis of a novel missense mutation in GATA3 causing hypoparathyroidism, sensorineural deafness and renal dysplasia syndrome in a Chinese family.
Purpose: Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant genetic disease associated with mutations in the GATA3 gene, which encodes GATA3 that plays essential roles in vertebrate development. This study aimed to identify and report the pathogenic mutation in GATA3 in a Chinese family diagnosed with HDR syndrome and determine its functional impacts in vivo.
Subjects and methods: The clinical features of a 25-year-old male patient with HDR syndrome and his parents were collected. GATA3 gene exome sequencing and Sanger sequencing were performed on the proband and his family, respectively. Functional analyses of GATA3 were performed using bioinformatics tools and zebrafish assays to determine pathogenicity and phenotype spectrum.
Results: A novel, heterozygous, missense mutation in exon 4 of the GATA3 gene, c.863 G > A, p.Cys288Tyr, in the proband and his mother who presented the complete HDR triad, was predicted to be deleterious by in silico tools. 3D structure modeling showed that the variant caused significant structural changes. In vivo studies using a zebrafish animal model revealed the deleterious impact of the variant on the gill buds, otoliths, and pronephros.
Conclusion: We identified a novel missense mutation, GATA3 p.Cys288Tyr, within a family with HDR syndrome and delineated it as a loss-of-function variant in vivo. This expands the spectrum of GATA3 mutations associated with HDR syndrome in the Chinese population and mimics HDR-related changes in vivo.
期刊介绍:
Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology.
Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted.
Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.