Genotype and Phenotype of 21-Hydroxylase Deficiency: A Single Center Experience from Western India.

IF 1.7 4区医学 Q2 PEDIATRICS

Indian pediatrics Pub Date : 2024-10-15 Epub Date: 2024-07-23

Manjiri Karlekar, Rohit Barnabas, Vijaya Sarathi, Anurag Lila, Sneha Arya, Samiksha Hegishte, Vishwambhar V Bhandare, Saba Samad Memon, Virendra Patil, Tushar Bandgar, Ambarish Kunwar, Nalini Shah

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引用次数: 0

Abstract

Objective: To describe the genotype-phenotype characteristics of patients with 21-hydroxylase deficiency from western India and ascertain the prevalence of various phenotypes of 21-hydroxylase deficiency.

Methods: Patients with 21-hydroxylase deficiency, diagnosed clinically and biochemically, were prospectively enrolled and classified into salt wasting (SW), simple virilizing (SV), and non-classic (NC) phenotypes and were subjected to genetic testing of CYP21A2 by targeted sequencing and multiplex ligation-dependent probe amplification (MLPA).

Results: Eighty (64; 46, XX) probands with 21-hydroxylase deficiency were analyzed. 41 had SW, 34 had SV, and 5 had NC phenotype. Disease-causing mutations were identified in 158/160 alleles. The common mutations were Deletions/Large Gene Conversions (Del/LGC, 25.6%), p.293-13A/C>G (22.5%), and p.Ile173Asn(18.75%). Exon 6 cluster mutations (Ile236Asn, Val237Glu, Met238Lys) and p.Val282Leu were absent. c.-113G>A+p.Pro31Leu (6.87%) and p.Phe405Ser (2.5%) were rare recurrent mutations with a possible founder effect. Two novel variants (Exon 1, p.Leu49Arg, Exon 8, p.Leu362Ter) were identified and were estimated to have low enzyme activity (<2%).

Conclusion: Del/LGC were the most common mutations identified. The c.-113G>A+p.Pro31Leu and p.Phe405Ser were recurrent variants with possible founder effect. This study also reiterates the low prevalence of NC CAH in Indian cohorts.

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21 型羟化酶缺乏症的基因型和表型：印度西部单中心经验

目的描述印度西部 21- 羟化酶缺乏症患者的基因型-表型特征，并确定 21- 羟化酶缺乏症各种表型的患病率：方法：对经临床和生化确诊的21-羟化酶缺乏症患者进行前瞻性登记，将其分为盐消瘦（SW）、单纯男性化（SV）和非经典（NC）表型，并通过靶向测序和多重连接依赖性探针扩增（MLPA）对CYP21A2进行基因检测：结果：对 80 名（64；46，XX）21-羟化酶缺乏症患者进行了分析。41例为SW型，34例为SV型，5例为NC型。在 158/160 个等位基因中发现了致病突变。常见突变为缺失/大基因转换（Del/LGC，25.6%）、p.293-13A/C>G（22.5%）和p.Ile173Asn（18.75%）。c.-113G>A+p.Pro31Leu（6.87%）和p.Phe405Ser（2.5%）是罕见的复发性突变，可能存在创始人效应。发现了两个新变异（外显子 1，p.Leu49Arg；外显子 8，p.Leu362Ter），估计其酶活性较低（结论：Del/LGC 是最常见的基因突变：Del/LGC是最常见的突变。c.-113G>A+p.Pro31Leu和p.Phe405Ser是反复出现的变异，可能存在创始人效应。这项研究还重申了印度队列中 NC CAH 的低患病率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Indian pediatrics 医学-小儿科

CiteScore

3.30

自引率

8.70%

发文量

344

审稿时长

3-8 weeks

期刊介绍： The general objective of Indian Pediatrics is "To promote the science and practice of Pediatrics." An important guiding principle has been the simultaneous need to inform, educate and entertain the target audience. The specific key objectives are: -To publish original, relevant, well researched peer reviewed articles on issues related to child health. -To provide continuing education to support informed clinical decisions and research. -To foster responsible and balanced debate on controversial issues that affect child health, including non-clinical areas such as medical education, ethics, law, environment and economics. -To achieve the highest level of ethical medical journalism and to produce a publication that is timely, credible and enjoyable to read.