オオトモ　タカノブ   Takanobu Otomo   大友　孝信    所属   川崎医科大学  医学部 基礎医学　分子遺伝医学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	A novel nonsense variant in ARID1B causing simultaneous RNA decay and exon skipping is associated with Coffin-Siris syndrome.
掲載誌名	正式名：Human genome variation 略　 称：Hum Genome Var ISSNコード：2054345X/2054345X
掲載区分	国外
巻・号・頁	9(1),pp.26
著者・共著者	Sofronova Viktoriia, Fukushima Yu, Masuno Mitsuo, Naka Mami, Nagata Miho, Ishihara Yasuki, Miyashita Yohei, Asano Yoshihiro, Moriwaki Takahito, Iwata Rina, Terawaki Seigo, Yamanouchi Yasuko, Otomo Takanobu
発行年月	2022/07/25
概要	Coffin-Siris syndrome (CSS) is a congenital disorder that is characterized by an absent/hypoplastic fifth distal phalanx, psychomotor developmental delay, and coarse facial features. One of the causative genes, ARID1B (AT-rich interactive domain-containing protein 1B), encodes components of the BAF chromatin remodeling complexes. Here, we report a case of a 3-year 8-month-old male with a novel nonsense variant (NM_001374820.1:c.4282C > T, p.(Gln1428*)) in the ARID1B gene, which was identified with whole-exome sequencing. He showed clinical symptoms of cleft soft palate, distinctive facial features (flat nasal bridge, thick eyebrows, and long eyelashes), right cryptorchidism, and hypertrichosis that partially overlapped with CSS. One of the most characteristic features of CSS is absent/hypoplastic fifth distal phalanx. He showed no obvious clinical finding in the lengths of his fingers or in the formation of his fingernails. However, radiographic analyses of the metacarpophalangeal bones revealed shortening of all the distal phalanges and fifth middle phalanges, suggesting brachydactyly. We performed mRNA analyses and revealed that both nonsense-mediated decay and nonsense-associated altered splicing were simultaneously caused by the c.4282C > T nonsense variant. The proband's clinical manifestations fit the previously reported criteria of disease for CSS or intellectual disability with ARID1B variant. Altogether, we suggest that c.4282C > T is a pathogenic variant that causes this clinical phenotype.
DOI	10.1038/s41439-022-00203-y
PMID	35879281