Novel SKIC3 variants in tricho-hepato-enteric syndrome with hemochromatosis

Kayo Ochiai; Yoshinori Aoki; Naoshi Yamada; Murasaki Aman; Atsushi Yamashita; Masatoshi Yamaguchi; Daisuke Nakato; Toshiki Takenouchi; Kenjiro Kosaki; Yuki Kodama; Hiroshi Moritake

doi:10.1038/s41439-025-00318-y

Novel SKIC3 variants in tricho-hepato-enteric syndrome with hemochromatosis

Hum Genome Var. 2025 Jul 18;12(1):14. doi: 10.1038/s41439-025-00318-y.

Authors

Kayo Ochiai^{1

2}, Yoshinori Aoki^{3

4}, Naoshi Yamada^{2

5}, Murasaki Aman⁶, Atsushi Yamashita⁶, Masatoshi Yamaguchi⁷, Daisuke Nakato⁸, Toshiki Takenouchi⁹, Kenjiro Kosaki⁸, Yuki Kodama^{2

5}, Hiroshi Moritake¹

Affiliations

¹ Division of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
² Perinatal Center, University of Miyazaki Hospital, Miyazaki, Japan.
³ Division of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. yoshinori_aoki@med.miyazaki-u.ac.jp.
⁴ Perinatal Center, University of Miyazaki Hospital, Miyazaki, Japan. yoshinori_aoki@med.miyazaki-u.ac.jp.
⁵ Obstetrics & Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
⁶ Division of Pathophysiology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
⁷ Division of Clinical Genetics, University of Miyazaki, Miyazaki, Japan.
⁸ Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
⁹ Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Abstract

Tricho-hepato-enteric syndrome (THES), a rare autosomal recessive disorder caused by variants in the SKIC3 or SKIC2 gene, is characterized by intractable diarrhea, woolly hair, growth restriction and liver disease. Here we report a neonatal case of THES with neonatal hemochromatosis, in which the novel compound heterozygous SKIC3 variants NM_014639.4:c.815_816del p.(Gly272AlafsTer9) and NM_014639.4:c.2284G>A p.(Gly762Arg) were identified. Further research is needed to elucidate the mechanisms underlying iron metabolism dysregulation in THES.

Abstract

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