Ran Li, Yiying Yang, Xudong Bao, Meiping Chen, Hongbo Yang, Fengying Gong, Hanze Du, Hui Pan, Huijuan Zhu
{"title":"孤立生长激素缺乏症 I 型和 II 型的遗传变异、临床表现和治疗结果：病例系列和文献综述。","authors":"Ran Li, Yiying Yang, Xudong Bao, Meiping Chen, Hongbo Yang, Fengying Gong, Hanze Du, Hui Pan, Huijuan Zhu","doi":"10.1007/s12020-024-04102-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To report a case series of four patients with isolated growth hormone deficiency (IGHD) type I from two Chinese pedigrees and to elucidate phenotype-genotype correlation of IGHD type I and II with GH1 gene alterations in the literature.</p><p><strong>Methods: </strong>Whole exome sequencing (WES) was performed and a literature review was conducted.</p><p><strong>Results: </strong>Four patients presented with extreme growth retardation (height -4.74 to -6.50 SDS) and undetectable peak growth hormone (GH) during GH stimulating test. WES revealed a novel homozygous nonsense mutation, c.316delC (p.L106Cfs*35), in GH1 gene in the the first pedigree. Deletions of exon 1-5 in GH1 gene were identified in the second pedigree. Ideal catch-up growth after GH treatment was achieved. 94 patients with IGHD type I and 240 patients with IGHD type II were included in literature review. Patients with IGHD type I exhibited younger age (3.2 vs 6.0 years, P < 0.001), more severe growth retardation (median height -6.50 vs -3.84 SDS, P < 0.001), lower peak GH levels (0.05 vs 1.70 ng/ml, P < 0.001) and a higher dosage of GH (0.22 vs 0.17 mg/kg/week, P = 0.012) compared to patients with IGHD type II. Gross deletions constituted 72.3% of IGHD type I cases, while splicing mutations and missense mutations comprised 54.2% and 45.0% of IGHD type II cases. In patients with IGHD type I harboring gross deletion, an early age of diagnosis correlated with both a higher height SDS at diagnosis and a better response after GH treatment. Height SDS after GH treatment in patients with IGHD type II carrying splicing mutations was negatively correlated with age at diagnosis.</p><p><strong>Conclusion: </strong>We identified two GH1 gene mutations, c.316delC (p.L106Cfs*35) and deletions of exon 1-5 in four Chinese patients with IGHD type I. They had a good response to GH treatment and gained satisfactory height improvement. Early diagnosis and initiating treatment may lead to a better prognosis.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetic variations, clinical presentation and treatment outcome of isolated growth hormone deficiency type I and II: case series and review of the literature.\",\"authors\":\"Ran Li, Yiying Yang, Xudong Bao, Meiping Chen, Hongbo Yang, Fengying Gong, Hanze Du, Hui Pan, Huijuan Zhu\",\"doi\":\"10.1007/s12020-024-04102-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To report a case series of four patients with isolated growth hormone deficiency (IGHD) type I from two Chinese pedigrees and to elucidate phenotype-genotype correlation of IGHD type I and II with GH1 gene alterations in the literature.</p><p><strong>Methods: </strong>Whole exome sequencing (WES) was performed and a literature review was conducted.</p><p><strong>Results: </strong>Four patients presented with extreme growth retardation (height -4.74 to -6.50 SDS) and undetectable peak growth hormone (GH) during GH stimulating test. WES revealed a novel homozygous nonsense mutation, c.316delC (p.L106Cfs*35), in GH1 gene in the the first pedigree. Deletions of exon 1-5 in GH1 gene were identified in the second pedigree. Ideal catch-up growth after GH treatment was achieved. 94 patients with IGHD type I and 240 patients with IGHD type II were included in literature review. Patients with IGHD type I exhibited younger age (3.2 vs 6.0 years, P < 0.001), more severe growth retardation (median height -6.50 vs -3.84 SDS, P < 0.001), lower peak GH levels (0.05 vs 1.70 ng/ml, P < 0.001) and a higher dosage of GH (0.22 vs 0.17 mg/kg/week, P = 0.012) compared to patients with IGHD type II. Gross deletions constituted 72.3% of IGHD type I cases, while splicing mutations and missense mutations comprised 54.2% and 45.0% of IGHD type II cases. In patients with IGHD type I harboring gross deletion, an early age of diagnosis correlated with both a higher height SDS at diagnosis and a better response after GH treatment. Height SDS after GH treatment in patients with IGHD type II carrying splicing mutations was negatively correlated with age at diagnosis.</p><p><strong>Conclusion: </strong>We identified two GH1 gene mutations, c.316delC (p.L106Cfs*35) and deletions of exon 1-5 in four Chinese patients with IGHD type I. They had a good response to GH treatment and gained satisfactory height improvement. Early diagnosis and initiating treatment may lead to a better prognosis.</p>\",\"PeriodicalId\":11572,\"journal\":{\"name\":\"Endocrine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-11-19\",\"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/s12020-024-04102-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12020-024-04102-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
Genetic variations, clinical presentation and treatment outcome of isolated growth hormone deficiency type I and II: case series and review of the literature.
Purpose: To report a case series of four patients with isolated growth hormone deficiency (IGHD) type I from two Chinese pedigrees and to elucidate phenotype-genotype correlation of IGHD type I and II with GH1 gene alterations in the literature.
Methods: Whole exome sequencing (WES) was performed and a literature review was conducted.
Results: Four patients presented with extreme growth retardation (height -4.74 to -6.50 SDS) and undetectable peak growth hormone (GH) during GH stimulating test. WES revealed a novel homozygous nonsense mutation, c.316delC (p.L106Cfs*35), in GH1 gene in the the first pedigree. Deletions of exon 1-5 in GH1 gene were identified in the second pedigree. Ideal catch-up growth after GH treatment was achieved. 94 patients with IGHD type I and 240 patients with IGHD type II were included in literature review. Patients with IGHD type I exhibited younger age (3.2 vs 6.0 years, P < 0.001), more severe growth retardation (median height -6.50 vs -3.84 SDS, P < 0.001), lower peak GH levels (0.05 vs 1.70 ng/ml, P < 0.001) and a higher dosage of GH (0.22 vs 0.17 mg/kg/week, P = 0.012) compared to patients with IGHD type II. Gross deletions constituted 72.3% of IGHD type I cases, while splicing mutations and missense mutations comprised 54.2% and 45.0% of IGHD type II cases. In patients with IGHD type I harboring gross deletion, an early age of diagnosis correlated with both a higher height SDS at diagnosis and a better response after GH treatment. Height SDS after GH treatment in patients with IGHD type II carrying splicing mutations was negatively correlated with age at diagnosis.
Conclusion: We identified two GH1 gene mutations, c.316delC (p.L106Cfs*35) and deletions of exon 1-5 in four Chinese patients with IGHD type I. They had a good response to GH treatment and gained satisfactory height improvement. Early diagnosis and initiating treatment may lead to a better prognosis.
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.
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