Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Department of Pediatric Neurology, Fukuoka Children's Hospital, Fukuoka, Japan.
Hum Genet. 2022 Nov;141(11):1771-1784. doi: 10.1007/s00439-022-02437-w. Epub 2022 May 3.
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 had MTOR variant (36%) and another had an RHOA variant. De novo germline variants in USP9X, TFE3, and KCNQ5 were detected in two, one, and one patients, respectively. A maternally inherited PHF6 variant was detected in one patient with hyperpigmented skin. Compound heterozygous GTF3C5 variants 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.
伊藤色素不均型，又称伊藤色素减退症，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，最近也有少数单基因引起的色素镶嵌病例报道。本研究招募了 11 名色素镶嵌症（主要为皮肤色素减退）的无关个体。采集先证者的皮肤打孔活检和基于三个人的血液样本（来自先证者及其双亲），提取基因组 DNA 并进行外显子组测序分析。在所有患者中，均发现了可能的单基因原因，分别在 5 名和 6 名患者中发现了体细胞和种系变异。在体细胞变异中，4 名患者携带 MTOR 变异（36%），另一名患者携带 RHOA 变异。在 2 名、1 名和 1 名患者中分别发现了 USP9X、TFE3 和 KCNQ5 的新生种系变异。一名皮肤色素沉着过度的患者携带 PHF6 变异，为母系遗传。在其余一名患者中，GTF3C5 的复合杂合变异被确定为强候选原因。建议使用患者的血液和皮肤样本进行外显子组测序，作为检测色素镶嵌症致病遗传变异的首选方法。
