Genetic variations, clinical presentation and treatment outcome of isolated growth hormone deficiency type I and II: case series and review of the literature.

IF 3.7 3区医学 Q2 Medicine

Endocrine Pub Date : 2024-11-19 DOI:10.1007/s12020-024-04102-w

Ran Li, Yiying Yang, Xudong Bao, Meiping Chen, Hongbo Yang, Fengying Gong, Hanze Du, Hui Pan, Huijuan Zhu

{"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":"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.","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}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

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。

目的：报告来自两个中国血统的四例孤立性生长激素缺乏症（IGHD）I型患者的系列病例，并阐明文献中IGHD I型和II型与GH1基因改变的表型-基因型相关性：方法：进行了全外显子组测序（WES），并进行了文献综述：结果：四名患者出现极度生长迟缓（身高-4.74至-6.50 SDS），且在促生长激素试验中检测不到生长激素峰值。WES 发现第一个血统中的 GH1 基因有一个新的同基因无义突变，即 c.316delC (p.L106Cfs*35)。第二个血统中发现了 GH1 基因 1-5 号外显子的缺失。经 GH 治疗后，患者实现了理想的追赶性生长。文献综述包括94名IGHD I型患者和240名IGHD II型患者。IGHD I型患者年龄较小（3.2岁对6.0岁，P我们在四名中国 IGHD I 型患者中发现了两个 GH1 基因突变，即 c.316delC (p.L106Cfs*35) 和 1-5 号外显子缺失。早期诊断和开始治疗可改善预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Endocrine 医学-内分泌学与代谢

CiteScore

6.40

自引率

5.40%

发文量

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.