Department of Urology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Gastroenterology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
BMC Med Genomics. 2022 Aug 15;15(1):178. doi: 10.1186/s12920-022-01334-5.
Disorders of sex development (DSD) are congenital disorders in which the development of the chromosomal, gonadal, or anatomical sex is atypical. Mutations in various genes can impede gonadal development, hormone synthesis, or hormone function and cause DSD.
Exome sequencing was performed for two siblings with 46,XY DSD. All mutations identified by exome sequencing were confirmed by Sanger sequencing.
The 13-month-old younger sibling had a female appearance of the external genital with a clitoris that was assessed as Prader III and scored 2 in the external masculinization score evaluative test. The 16-year-old elder sibling had severe hypospadias. Exome sequencing revealed compound heterozygous mutations in exon 3 of DHH in the siblings with 46,XY DSD. The frameshift mutation (NM_021044.3: c.602delC) was derived from the father and was predicted to be deleterious. The (c.937G > T) substitution mutation was derived from the mother.
Novel compound heterozygous mutations of DHH led to 46,XY DSD in two siblings. This study expands the phenotypic mutation spectra of DHH in patients with 46,XY DSD.
性发育障碍（DSD）是一种先天性疾病，其染色体、性腺或解剖性别发育异常。各种基因突变可阻碍性腺发育、激素合成或激素功能，导致 DSD。
对 2 例 46,XY DSD 同胞进行外显子组测序。通过外显子组测序鉴定的所有突变均通过 Sanger 测序确认。
13 月龄的弟弟外生殖器呈女性外观，阴蒂评估为 Prader III，外部男性化评分评估试验得分为 2。16 岁的哥哥患有严重的尿道下裂。外显子组测序显示，患有 46,XY DSD 的同胞存在 DHH 外显子 3 的复合杂合突变。移码突变（NM_021044.3：c.602delC）来自父亲，预测为有害。（c.937G>T）取代突变来自母亲。
DHH 的新复合杂合突变导致 2 例 46,XY DSD。本研究扩展了 46,XY DSD 患者 DHH 的表型突变谱。
