A homozygous G insertion in MPLKIP leads to TTDN1 with the hypergonadotropic hypogonadism symptom
A homozygous G insertion in MPLKIP leads to TTDN1 with the hypergonadotropic hypogonadism symptom
复制标题
MPLKIP 中的纯合 G 插入导致 TTDN1 出现高促性腺激素性性腺功能减退症症状
DOI：
10.1186/s12881-018-0723-5
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发表时间：
2018-12-31
影响因子：
--
通讯作者：
Zheng, Yun
中科院分区：
文献类型：
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作者：
Zhou, Yi-Kun;Yang, Xiao-Chun;Zheng, Yun
研究背景非光敏性毛发硫营养不良1（Trichothiodystrophy non-photosensitive 1，TTDN 1）是一种以智力低下、毛发脆化为特征的疾病。方法对1例女性高促性腺激素性性腺功能减退症患者的临床特征、发干硫含量及发干类型进行了详细的分析，并与其健康的父母、兄弟进行了比较。我们还收集了患者的血液样本并进行了外显子测序。在分析获得的外显子测序谱后，在MPLKIP中鉴定出一个G插入。使用桑格测序验证患者、其父母和兄弟的G插入位点。结果TTDN 1的女性患者在MPLKIP基因中携带一个纯合的G插入（rs747470385）。患者的父母和兄弟是同一突变的杂合子携带者，但健康。患者的毛干呈虎尾状，硫含量相对较低。据我们所知，这是第一个报告，常染色体隐性遗传的G插入MPLKIP基因导致TTDN 1。结论我们的研究结果表明，纯合子的G插入MPLKIP导致TTDN 1高促性腺激素性功能减退症，而同一突变的杂合子携带者没有症状和健康。这些结果为MPLKIP和TTDN 1突变与高促性腺激素性性腺功能减退症的关联提供了新的见解。
BackgroundTrichothiodystrophy nonphotosensitive 1 (TTDN1) is a disease with mental retardation, brittle hair. Some cases of the diseases are caused by mutations of the MPLKIP gene.MethodsWe carefully identified the clinic characteristics, the sulfur level and pattern of the hair shafts of a female patient of with the symptom of hypergonadotropic hypogonadism, and of her parents and brother whose are healthy. We also collected the blood sample of the patient and performed the exon sequencing. One G insertion in MPLKIP was identified after analyzing the obtained exon sequencing profile. The G insertion sites in the patient, her parents and brother, were verified using Sanger sequencing. The G insertion in MPLKIP were compared to the dbSNP.ResultsThe female patient of TTDN1 carries a homozygous G insertion (rs747470385) in the MPLKIP gene. The parents and brother of the patient are heterozygous carriers of the same mutation, but are healthy. The hair shafts of the patient had a tiger-tail pattern with relatively low sulfur levels. To the best of our knowledge, this is the first report that autosomal recessive inheritance of the G insertion in the MPLKIP gene results in TTDN1.ConclusionOur results indicate that the homozygotic G insertion in MPLKIP results in the TTDN1 with hypergonadotropic hypogonadism, while heterozygous carriers of the same mutation have no symptoms and healthy. These results provide novel insights into the association of mutations in MPLKIP and TTDN1 with hypergonadotropic hypogonadism.