Department of Endocrinology, Genetics, Metabolism and Adolescent Medicine, Beijing Children's Hospital, The Capital Medical University, National Center for Children's Health, Beijing, China.
Front Endocrinol (Lausanne). 2020 Dec 23;11:582516. doi: 10.3389/fendo.2020.582516. eCollection 2020.
Mastermind-like domain-containing 1 (MAMLD1) has been shown to play an important role in the process of sexual development and is associated with 46,XY disorders of sex development (DSDs). However, the causative role of variations in DSDs remains disputable. In this study, we have described a clinical series on children from unrelated families with 46,XY DSD harbouring variants. Whole exome sequencing (WES) was performed for each patient. WES data were filtered using common tools and disease customisation algorithms, including comparison against lists of known and candidate MAMLD1-related and DSD-related genes. Lastly, we investigated the hypothesis that MAMLD1-related DSD may follow an oligogenic mode of inheritance. Forty-three potentially deleterious/candidate variants of 18 genes (, , , , , , , , , , , , , , , , , and ) were identified, which may have contributed to the patient phenotypes. was the most commonly identified gene. Specific gene combinations were also identified. In the interactome analysis, exhibited direct connection with // and /. Through , the following eight genes were shown to be associated with :, , , , , and . Our findings provide further evidence that individuals with MAMLD1-related 46,XY DSD could carry two or more variants of known DSD-related genes, and the phenotypic outcome of affected individuals might be determined by multiple genes.
类泛素化酶域蛋白 1（MAMLD1）在性发育过程中发挥着重要作用，与 46,XY 性别发育障碍（DSD）有关。然而，DSD 变异的因果作用仍存在争议。在这项研究中，我们描述了一组来自无关家庭的 46,XY DSD 患儿的临床系列，这些患儿携带变异。对每位患者进行了外显子组测序（WES）。使用常见工具和疾病定制算法对 WES 数据进行过滤，包括与已知和候选 MAMLD1 相关和 DSD 相关基因列表进行比较。最后，我们研究了 MAMLD1 相关 DSD 是否可能遵循寡基因遗传模式的假设。鉴定出 18 个基因（、、、、、、、、、、、、、、、和）的 43 个潜在有害/候选变异，这些变异可能导致了患者的表型。是最常鉴定出的基因。还确定了特定的基因组合。在相互作用分析中，显示与//和/直接连接。通过，以下八个基因与相关：、、、、、和。我们的发现进一步证明，携带 MAMLD1 相关 46,XY DSD 的个体可能携带两个或多个已知 DSD 相关基因的变异，受影响个体的表型结果可能由多个基因决定。
