Normal early development in siblings with novel compound heterozygous variants in ASPM

Taro Moriwaki; Narutoshi Yamazaki; Tetsumin So; Motomichi Kosuga; Osamu Miyazaki; Yoko Narumi-Kishimoto; Tadashi Kaname; Gen Nishimura; Torayuki Okuyama; Yasuyuki Fukuhara

doi:10.1038/s41439-019-0088-0

Normal early development in siblings with novel compound heterozygous variants in ASPM

Hum Genome Var. 2020 Jan 6:6:56. doi: 10.1038/s41439-019-0088-0. eCollection 2019.

Authors

Affiliations

¹ 1Division of Medical Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 Japan.
² 2Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 Japan.
³ 3Division of Critical Care Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 Japan.
⁴ 4Department of Radiology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 Japan.
⁵ 5Medical Genome Center, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 Japan.
⁶ 6Department of Genome Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 Japan.
⁷ 7Center of Intractable Diseases, Saitama Medical University Hospital, Saitama, Japan.

Abstract

Autosomal recessive primary microcephaly 5 (MCPH5) is caused by pathogenic variants in ASPM. Using whole-exome sequencing, we diagnosed two siblings with MCPH5. A known pathogenic variant (NM_018136.4: c.9697C > T, p.(Arg3233*)) and a novel pathogenic variant (c.1402_1406del, p.(Asn468Serfs*2)) of ASPM were identified in affected siblings with normal intelligence. Their pathogenic variants were not located in the critical regions of ASPM, but the relationship between the genotypes and their normal intelligence was unclear.

Keywords: Disease genetics; Diseases.