Distal arthrogryposis in a girl arising from a novel TNNI2 variant inherited from paternal somatic mosaicism
Distal arthrogryposis in a girl arising from a novel TNNI2 variant inherited from paternal somatic mosaicism
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女孩的远端关节弯曲是由父系体细胞嵌合体遗传的新型 TNNI2 变异引起的
DOI：
10.1038/s10038-022-01117-x
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发表时间：
2023
期刊：
影响因子：
3.5
通讯作者：
N. Okamoto and N. Matsumoto
中科院分区：
文献类型：
--
作者：
R. Seyama;Y. Uchiyama;Y. Kaneshi;K. Hamanaka;A. Fujita;N. Tsuchida;E. Koshimizu;K. Misawa;S. Miyatake;T. Mizuguchi;S. Makino;A. Itakura;N. Okamoto and N. Matsumoto
TnNI2at 11p15.5编码肌钙蛋白I2，属于肌钙蛋白I基因家族的一员，是肌钙蛋白复合体的组成部分。远端关节紊乱病(DA)的特征是先天性肢体痉挛，没有原发的神经或肌肉影响。DA以常染色体显性方式遗传，在临床和遗传上是异质性的。外显子组测序发现1例典型DA2b日本女孩的TNNI2[NM_003282.4：C.532T>；C p.(Phe178Leu)]存在致病变异。有趣的是，使用桑格测序的家族研究表明，她健康的父亲体内存在马赛克变异。随后的定向扩增深度测序在父亲的外周血白细胞、唾液、头发和指甲的基因组DNA中检测到TNNI2变异，变异等位基因频率为9.4-17.7%。我们证实了先证者的TNNI2基因中的一个致病变异，该变异来自于她无症状的父亲及其体细胞变异。我们的病例表明，在DA中需要仔细的临床和基因评估。
TNNI2at 11p15.5 encodes troponin I2, fast skeletal type, which is a member of the troponin I gene family and a component of the troponin complex. Distal arthrogryposis (DA) is characterized by congenital limb contractures without primary neurological or muscular effects. DA is inherited in an autosomal dominant fashion and is clinically and genetically heterogeneous. Exome sequencing identified a causative variant inTNNI2[NM_003282.4:c.532T>C p.(Phe178Leu)] in a Japanese girl with typical DA2b. Interestingly, the familial study using Sanger sequencing suggested a mosaic variant in her healthy father. Subsequent targeted amplicon-based deep sequencing detected theTNNI2variant with variant allele frequencies of 9.4–17.7% in genomic DNA derived from peripheral blood leukocytes, saliva, hair, and nails in the father. We confirmed a disease-causing variant inTNNI2in the proband inherited from her asymptomatic father with its somatic variant. Our case demonstrates that careful clinical and genetic evaluation is required in DA.