Monogenic causes of pigmentary mosaicism
Monogenic causes of pigmentary mosaicism
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DOI：
10.1007/s00439-022-02437-w
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发表时间：
2022-05
期刊：
影响因子：
5.3
通讯作者：
K. Saida;P. Chong;A. Yamaguchi;Naka Saito;Hajime Ikehara;E. Koshimizu;R. Miyata;A. Ishiko;Kazuyuki Nakamura;H. Ohnishi;K. Fujioka;T. Sakakibara;H. Asada;K. Ogawa;K. Kudo;Eri Ohashi;M. Kawai;Yuichi Abe;N. Tsuchida;Yuri Uchiyama;K. Hamanaka;A. Fujita;T. Mizuguchi;S. Miyatake;N. Miyake;Mitsuhiro Kato;R. Kira;N. Matsumoto
中科院分区：
文献类型：
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作者：
K. Saida;P. Chong;A. Yamaguchi;Naka Saito;Hajime Ikehara;E. Koshimizu;R. Miyata;A. Ishiko;Kazuyuki Nakamura;H. Ohnishi;K. Fujioka;T. Sakakibara;H. Asada;K. Ogawa;K. Kudo;Eri Ohashi;M. Kawai;Yuichi Abe;N. Tsuchida;Yuri Uchiyama;K. Hamanaka;A. Fujita;T. Mizuguchi;S. Miyatake;N. Miyake;Mitsuhiro Kato;R. Kira;N. Matsumoto
伊藤型色素嵌合体，也称为伊藤黑色素减少症，是一种神经皮肤综合征，被认为主要由体细胞染色体嵌合体引起。然而，最近报道了一些单基因的色素嵌合体的原因。本研究招募了11名患有色素镶嵌症（主要是色素减退皮肤）的无关个体。收集先证者的皮肤穿刺活检和基于trio的血液样品（来自先证者和生物学父母），提取基因组DNA并通过外显子组测序进行分析。在所有患者中，检测到可能的单基因原因，分别在5名和6名患者中鉴定出体细胞和生殖系变异。在体细胞变异中，4例患者有MTOR变异（36%），另1例有RHOA变异。在2例、1例和1例患者中分别检测到USP9X、TFE3和KCNQ5的从头生殖系变异。在一名色素沉着皮肤患者中检测到一种母系遗传的PHF 6变体。在剩余的患者中，化合物异源GTF 3C5变体被强调为强有力的候选者。强烈推荐使用患者的血液和皮肤样本进行外显子组测序，作为检测色素嵌合体致病性遗传变异的首选。
Pigmentary mosaicism of the Ito type, also known as hypomelanosis of Ito, is a neurocutaneous syndrome considered to be predominantly caused by somatic chromosomal mosaicism. However, a few monogenic causes of pigmentary mosaicism have been recently reported. Eleven unrelated individuals with pigmentary mosaicism (mostly hypopigmented skin) were recruited for this study. Skin punch biopsies of the probands and trio-based blood samples (from probands and both biological parents) were collected, and genomic DNA was extracted and analyzed by exome sequencing. In all patients, plausible monogenic causes were detected with somatic and germline variants identified in five and six patients, respectively. Among the somatic variants, four patients hadMTORvariant (36%) and another had anRHOAvariant. De novo germline variants inUSP9X,TFE3, andKCNQ5were detected in two, one, and one patients, respectively. A maternally inheritedPHF6variant was detected in one patient with hyperpigmented skin. Compound heterozygousGTF3C5variants were highlighted as strong candidates in the remaining patient. Exome sequencing, using patients’ blood and skin samples is highly recommended as the first choice for detecting causative genetic variants of pigmentary mosaicism.