Loss-of-function mutations in TDRD7 lead to a rare novel syndrome combining congenital cataract and nonobstructive azoospermia in humans
Loss-of-function mutations in TDRD7 lead to a rare novel syndrome combining congenital cataract and nonobstructive azoospermia in humans
复制标题
TDRD7 的功能丧失突变导致人类先天性白内障和非梗阻性无精子症相结合的罕见新综合征
DOI：
10.1038/gim.2017.130
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发表时间：
2019-05-01
影响因子：
8.8
通讯作者：
Lin, Ge
中科院分区：
文献类型：
--
作者：
Tan, Yue-Qiu;Tu, Chaofeng;Lin, Ge
PurposeComorbid familial nonobstructive azoospermia (NOA) and congenital cataract (CC) have not been reported previously, and no single human gene has been associated with both diseases in humans. Our purpose was to uncover novel human mutations and genes causing familial NOA and CC.MethodsWe performed whole-exome sequencing for two brothers with both NOA and CC from a consanguineous family. Mutation screening of TDRD7 was performed in another similar consanguineous family and 176 patients with azoospermia or CC alone and 520 healthy controls. Histological analysis was performed for the biopsied testicle sample in one patient, and knockout mice were constructed to verify the phenotype of the mutation in TDRD7.ResultsTwo novel loss-of-function mutations (c. 324_325insA (T110Nfs* 30) and c. 688_689insA (p. Y230X), respectively) of TDRD7 were found in the affected patients from the two unrelated consanguineous families. Histological analysis demonstrated a lack of mature sperm in the male patient’s seminiferous tubules. The mutations were not detected in patients with CC or NOA alone. Mice with Tdrd7 gene disrupted at a similar position precisely replicated the human syndrome.ConclusionWe identified TDRD7 causing CC as a new pathogenic gene for male azoospermia in human, with an autosomal recessive mode of inheritance.
