A novel splice site variant in ANOS1 gene leads to Kallmann syndrome in three siblings
A novel splice site variant in ANOS1 gene leads to Kallmann syndrome in three siblings
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DOI：
10.1016/j.gene.2019.144177
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发表时间：
2020-02-05
期刊：
影响因子：
3.5
通讯作者：
Shen, Ying
中科院分区：
文献类型：
--
作者：
Jiang, Xiaohui;Li, Dingming;Shen, Ying
特发性低促性腺激素性性腺功能减退症（IHH）是一种罕见的遗传性疾病，由低剂量的下丘脑促性腺激素释放激素（GnRH）引起，导致性发育缺失或延迟。Kallmann综合征（KS）以IHH伴嗅觉丧失或嗅觉减退为特征。在这里，我们确定了一个新的剪接位点变体（c。应用全外显子组测序技术（WES）检测了一个中国汉族KS家系3名同胞的ANOS1基因（726 + 2T > G）。在这个家庭中，KS被归类为X连锁隐性遗传模式。通过桑格测序，该突变遗传自母亲。体外功能实验证实了该突变对ANOS1基因转录水平的有害影响。重要的是，及时的激素替代治疗的有效性进行了评估的三个兄弟姐妹。因此，寻找遗传因素有助于KS的早期诊断和及时治疗。
Idiopathic hypogonadotropic hypogonadism (IHH) is a rare genetic disease caused by low doses of hypothalamic gonadotropin-releasing hormone (GnRH), leading to absence or delayed sexual development. Kallmann syndrome (KS) is characterized by IHH with anosmia or hyposmia. Here, we identified a novel splice site variant (c. 726 + 2T > G) of ANOS1 gene in three siblings with KS from a Chinese Han family by whole-exome sequencing (WES). In this family, KS is classified as an X-linked recessive inheritance pattern. This mutation was inherited from the mother by Sanger sequencing. An in vitro functional experiment has identified the deleterious effect of this mutation on the transcriptional level of ANOS1 gene. Importantly, the effectiveness of timely hormone replacement therapy was evaluated on the three siblings. Hence, finding genetic causes could be helpful in the early diagnosis and timely treatment of KS.