Consanguinity increases the risk of hereditary diseases including disorders of sex development (DSD). There are minimal data on DSD in the highly consanguineous population of Saudi Arabia. This study reports the molecular genetics of a series of patients with different types of DSD.

Methods

We enrolled 77 patients from 47 families with DSD. DNA was isolated from peripheral leucocytes. Genes of interest were amplified by polymerase chain reaction and subsequently sequenced.

Results

Overall, 77 patients from 47 families (44 of them are consanguineous) had a total of 29 mutations; 16 of them were described before and 13 were novel mutations. The most common condition was 5-α reductase deficiency (25 patients from 18 families) and the most common mutation was a splice site mutation in intron 1 (c.282-2 A > G). The next most common condition was 11-β hydroxylase (CYP11B1) deficiency where 19 patients from 10 families had 8 mutations (7 of them are novel). Other mutations affected CYP17A1 with 2 novel and 2 known mutations in 7 patients; HSD3B2 with 2 known mutations in 11 patients of 4 families; StAR with 1 novel and 1 known mutations in 4 patients; NR0B1 with 1 novel mutation in 2 siblings; HSD17B3 with 1 known mutation in 3 siblings; LHCGR with 1 novel mutation in 2 siblings; and AR with 1 novel and 3 known mutations in 4 unrelated patients.

Conclusion

In the highly consanguineous and homogeneous population of Saudi Arabia, SRD5A2 and CYP11B1 deficiencies are common causes of DSDs. Other DSDs occur less frequently but often with novel mutations.

中文翻译：

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高血缘人群中性发育障碍的分子遗传学。

血缘关系会增加遗传性疾病的风险，包括性发育障碍（DSD）。在高度血缘的沙特阿拉伯，关于DSD的数据很少。这项研究报告了一系列具有不同类型DSD的患者的分子遗传学。

方法

我们招募了来自47个DSD家庭的77名患者。从外周血白细胞分离DNA。通过聚合酶链反应扩增目的基因，然后进行测序。

结果

总体而言，来自47个家庭的77名患者（其中44名是近亲的）共有29个突变。其中16个在之前描述过，13个是新突变。最常见的情况是5-α还原酶缺乏症（来自18个家庭的25名患者），最常见的突变是内含子1的剪接位点突变（c.282-2 A> G）。下一个最常见的疾病是11-β羟化酶（CYP11B1）缺乏症，其中来自10个家庭的19位患者出现8个突变（其中7个是新突变）。其他突变影响CYP17A1的7例患者中有2个新突变和2个已知突变。HSD3B2在4个家庭的11位患者中具有2个已知的突变 有4例患者出现1例具有1个新突变和1个已知突变的StAR；NR0B12个同胞中有1个新突变；HSD17B3在3个同胞中具有1个已知突变；LHCGR在2个同胞中具有1个新突变；和AR 1个具有新颖性和4名无关患者3个的已知突变。

结论

在沙特阿拉伯的近亲和高度血缘人群中，SRD5A2和CYP11B1缺乏症是DSD的常见原因。其他DSD的发生频率较低，但经常具有新颖的突变。