A novel nonsense variant in ARID1B causing simultaneous RNA decay and exon skipping is associated with Coffin-Siris syndrome.

IF 1 Q4 GENETICS & HEREDITY
Viktoriia Sofronova, Yu Fukushima, Mitsuo Masuno, Mami Naka, Miho Nagata, Yasuki Ishihara, Yohei Miyashita, Yoshihiro Asano, Takahito Moriwaki, Rina Iwata, Seigo Terawaki, Yasuko Yamanouchi, Takanobu Otomo
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引用次数: 1

Abstract

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.

Abstract Image

ARID1B中一种新的无义变异引起同时的RNA衰变和外显子跳变与Coffin-Siris综合征有关。
Coffin-Siris综合征(CSS)是一种先天性疾病,其特征是第五远端指骨缺失/发育不良,精神运动发育迟缓,面部特征粗糙。其中一个致病基因ARID1B(富含at的相互作用结构域蛋白1B)编码BAF染色质重塑复合物的组分。在这里,我们报告了一例3岁8个月大的男性感染了一种新的无义变异(NM_001374820.1:c)。4282C > T, p.(Gln1428*)),通过全外显子组测序鉴定。临床表现为软腭裂,面部特征明显(鼻梁扁平,眉粗,睫毛长),右侧隐垂,多毛,与CSS部分重叠。CSS最典型的特征之一是第五远端指骨缺失/发育不良。他的手指的长度和指甲的形状没有明显的临床发现。然而,掌指骨的x线分析显示所有远端指骨和第五中指骨缩短,提示短指畸形。我们进行了mRNA分析,发现无义介导的衰变和无义相关的剪接改变同时由c.4282C > T无义变异引起。先证者的临床表现符合先前报道的伴有ARID1B变异的CSS或智力残疾的疾病标准。总之,我们认为c.4282C > T是导致这种临床表型的致病变异。
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来源期刊
Human Genome Variation
Human Genome Variation Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
2.30
自引率
0.00%
发文量
39
审稿时长
13 weeks
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