Monogenic causes of pigmentary mosaicism

Ken Saida¹, Pin Fee Chong², Asuka Yamaguchi³, Naka Saito⁴, Hajime Ikehara⁵, Eriko Koshimizu¹, Rie Miyata³, Akira Ishiko⁶, Kazuyuki Nakamura⁷, Hidenori Ohnishi⁸, Kei Fujioka⁹, Takafumi Sakakibara¹⁰, Hideo Asada¹¹, Kohei Ogawa¹¹, Kyoko Kudo¹², Eri Ohashi¹³, Michiko Kawai¹³, Yuichi Abe¹³, Naomi Tsuchida^{1

14}, Yuri Uchiyama^{1

14}, Kohei Hamanaka¹, Atsushi Fujita¹, Takeshi Mizuguchi¹, Satoko Miyatake^{1

15}, Noriko Miyake^{1

16}, Mitsuhiro Kato¹⁷, Ryutaro Kira², Naomichi Matsumoto¹⁸

Affiliations

¹ Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
² Department of Pediatric Neurology, Fukuoka Children's Hospital, Fukuoka, Japan.
³ Department of Pediatrics, Tokyo-Kita Medical Center, Tokyo, Japan.
⁴ Department of Pediatrics, Tsuruoka Municipal Shonai Hospital, Yamagata, Japan.
⁵ Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan.
⁶ Department of Dermatology, Toho University School of Medicine, Tokyo, Japan.
⁷ Department of Pediatrics, Faculty of Medicine, Yamagata University, Yamagata, Japan.
⁸ Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan.
⁹ Center of General Internal Medicine and Rheumatology, Gifu Municipal Hospital, Gifu, Japan.
¹⁰ Department of Pediatrics, Nara Medical University School of Medicine, Nara, Japan.
¹¹ Department of Dermatology, Nara Medical University School of Medicine, Nara, Japan.
¹² Department of Dermatology, Fukuoka Children's Hospital, Fukuoka, Japan.
¹³ Division of Neurology, National Center for Child Health and Development, Tokyo, Japan.
¹⁴ Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan.
¹⁵ Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Japan.
¹⁶ Department of Human Genetics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
¹⁷ Department of Pediatrics, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
¹⁸ Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. naomat@yokohama-cu.ac.jp.

PMID: 35503477
DOI: 10.1007/s00439-022-02437-w

Monogenic causes of pigmentary mosaicism

Ken Saida et al. Hum Genet. 2022 Nov.

. 2022 Nov;141(11):1771-1784.

doi: 10.1007/s00439-022-02437-w. Epub 2022 May 3.

Authors

Affiliations

¹ Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
² Department of Pediatric Neurology, Fukuoka Children's Hospital, Fukuoka, Japan.
³ Department of Pediatrics, Tokyo-Kita Medical Center, Tokyo, Japan.
⁴ Department of Pediatrics, Tsuruoka Municipal Shonai Hospital, Yamagata, Japan.
⁵ Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan.
⁶ Department of Dermatology, Toho University School of Medicine, Tokyo, Japan.
⁷ Department of Pediatrics, Faculty of Medicine, Yamagata University, Yamagata, Japan.
⁸ Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan.
⁹ Center of General Internal Medicine and Rheumatology, Gifu Municipal Hospital, Gifu, Japan.
¹⁰ Department of Pediatrics, Nara Medical University School of Medicine, Nara, Japan.
¹¹ Department of Dermatology, Nara Medical University School of Medicine, Nara, Japan.
¹² Department of Dermatology, Fukuoka Children's Hospital, Fukuoka, Japan.
¹³ Division of Neurology, National Center for Child Health and Development, Tokyo, Japan.
¹⁴ Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan.
¹⁵ Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Japan.
¹⁶ Department of Human Genetics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
¹⁷ Department of Pediatrics, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
¹⁸ Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. naomat@yokohama-cu.ac.jp.

PMID: 35503477
DOI: 10.1007/s00439-022-02437-w

Abstract

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.

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References

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Monogenic causes of pigmentary mosaicism

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Monogenic causes of pigmentary mosaicism

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