一名患有两种罕见综合征的突尼斯患者：三磷酸腺苷酶缺乏综合征和先天性低促性腺激素性性腺功能减退症。

A Tunisian patient with two rare syndromes: triple a syndrome and congenital hypogonadotropic hypogonadism.

作者信息

Cherif Ben Abdallah Lamia, Lakhoua Youssef, Nagara Majdi, Khiari Karima, Elouej Sahar, Messaoud Olfa, Bouyacoub Yosra, Romdhane Lilia, Turki Zinet, Abdelhak Sonia, Ben Abdallah Nejib

机构信息

LR11IPT05, Laboratoire de Génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, Université de Tunis El Manar, Tunis, Tunisia.

出版信息

Horm Res Paediatr. 2014;82(5):338-43. doi: 10.1159/000365888. Epub 2014 Sep 18.

DOI:10.1159/000365888

PMID:25247238

Abstract

BACKGROUND/AIMS: The coexistence of triple A syndrome (AAAS) and congenital hypogonadotropic hypogonadism (CHH) has so far not been reported in the literature. This study aimed to characterize at the clinical and genetic level one patient presenting an association of AAAS and CHH in order to identify causal mutations.

METHODS

Clinical and endocrinal investigations were performed and followed by mutational screening of candidate genes.

RESULTS

At the age of 18, the patient presented sexual infantilism, a micropenis and gynecomastia. No mutation was revealed in GnRHR, TACR3/TAC3, PROK2/PROKR2 and PROP1 genes, except a homozygous intronic variation (c.244 + 128C>T; dbSNP: rs350129) in the KISS1R gene, which is likely nondeleterious. A homozygous splice-donor site mutation (IVS14 + 1G>A) was found in the AAAS gene. This mutation, responsible for AAAS, is a founder mutation in North Africa.

CONCLUSION

This is the first report on a Tunisian patient with the coexistence of AAAS and CHH. The diagnosis of CHH should be taken in consideration in patients with Allgrove syndrome and who carry the IVS14 + 1G>A mutation as this might challenge appropriate genetic counseling.

摘要

背景/目的：文献中尚未报道过三 A 综合征（AAAS）与先天性低促性腺激素性性腺功能减退症（CHH）并存的情况。本研究旨在从临床和基因层面描述 1 例同时患有 AAAS 和 CHH 的患者，以确定致病突变。

方法

进行了临床和内分泌检查，随后对候选基因进行突变筛查。

结果

该患者 18 岁时出现性幼稚、小阴茎和乳腺增生。除了 KISS1R 基因中的一个纯合内含子变异（c.244 + 128C>T；dbSNP：rs350129）外，GnRHR、TACR3/TAC3、PROK2/PROKR2 和 PROP1 基因均未发现突变，该变异可能无有害影响。在 AAAS 基因中发现了一个纯合剪接供体位点突变（IVS14 + 1G>A）。这个导致 AAAS 的突变是北非的一个始祖突变。