Département de Génétique et Développement, Institut Cochin, Inserm U1016, Université Paris-Descartes, Paris, France.
Eur J Endocrinol. 2013 Oct 21;169(6):805-9. doi: 10.1530/EJE-13-0419. Print 2013 Dec.
Kallmann syndrome (KS) is a genetically heterogeneous developmental disorder that associates hypogonadotropic hypogonadism and anosmia. Various causative genes have been identified, but their respective involvement in different world regions is poorly documented.
We aimed to compare the prevalence of mutations in five routinely analyzed KS genes between Maghrebian and European patients.
Blood samples from 120 presumably unrelated Maghrebian patients were collected for DNA sequencing by the Sanger technique. The prevalence of the non-synonymous mutations in KAL1, FGFR1, FGF8, PROKR2, and PROK2 was determined for each gene, and compared with those previously obtained from the analysis of 712 European patients.
Diverse mutations in PROKR2, a gene involved both in monogenic recessive and digenic/oligogenic KS transmission modes, were found in 23.3% of the Maghrebian patients, but only in 5.1% of the European patients (Fisher's exact test, P<0.001), whereas mutations in each of the other four KS genes were present either at similar frequencies in the Maghrebian and European patients (KAL1, PROK2, FGF8, from 6.6 to 0.8%; Fisher's exact test, P>0.4 for all comparisons) or at a lower frequency in Maghrebian patients (FGFR1, 5.0 vs 11.7%; Fisher's exact test, P<0.05). Homozygosity resulting from consanguineous marriages was not sufficient to account for the greater prevalence of PROKR2 mutations in the Maghrebian patients.
The great prevalence of PROKR2 mutations in Maghrebian patients has practical consequences for molecular diagnosis of the disease and genetic counseling in the Maghrebian population.
卡尔曼综合征（KS）是一种遗传异质性发育障碍，与促性腺激素低下性性腺功能减退和嗅觉缺失有关。已经确定了各种致病基因，但它们在不同世界区域的各自参与情况记录甚少。
我们旨在比较五个常规分析的 KS 基因中的突变在马格里布和欧洲患者中的发生率。
采集了 120 名疑似无关的马格里布患者的血液样本，通过 Sanger 技术进行 DNA 测序。确定了每个基因中非同义突变在 KAL1、FGFR1、FGF8、PROKR2 和 PROK2 中的发生率，并与先前对 712 名欧洲患者分析所获得的发生率进行了比较。
在 23.3%的马格里布患者中发现了涉及单基因隐性和双基因/寡基因 KS 传播模式的 PROKR2 基因中的多种突变，但在 5.1%的欧洲患者中仅发现了这些突变（Fisher 确切检验，P<0.001），而其他四个 KS 基因中的突变在马格里布和欧洲患者中的发生率相似（KAL1、PROK2、FGF8，从 6.6%到 0.8%；Fisher 确切检验，所有比较的 P>0.4）或在马格里布患者中的发生率较低（FGFR1，5.0%对 11.7%；Fisher 确切检验，P<0.05）。由于近亲结婚导致的纯合性不足以解释马格里布患者中 PROKR2 突变的高发生率。
马格里布患者中 PROKR2 突变的高发生率对该疾病的分子诊断和马格里布人群的遗传咨询具有实际意义。
