Tamhankar Vasundhara, Tamhankar Parag, Chaubal Rajas, Chaubal Jyoti, Chaubal Nitin
Genetics, Centre for Medical Genetics, Mumbai, IND.
Genetics, MedGenome Labs, Bengaluru, IND.
Cureus. 2021 Nov 17;13(11):e19682. doi: 10.7759/cureus.19682. eCollection 2021 Nov.
The gene encodes THO complex subunit 2, a subunit of the Transcription-Export (TREX) complex which binds specifically to splice messenger ribonucleic acid (mRNAs) to facilitate mRNA export. Mutations in the gene have been described to lead to X-linked mental retardation syndrome type 12/35 (XLMR-12/35) (MIM#300957). Here, we describe for the first time a recurrent arthrogryposis multiplex congenita phenotype (AMC) in two male fetuses in a family. Exome sequencing identified a novel pathogenic variation chrX: 122761817_122761820delTGAC (genome assembly GRCh37 format) or c.2482-1_2484delGTCA (as per Genbank transcript ID NM_001081550) in the gene. This variant affects the consensus acceptor splice site between intron 22 and exon 23. This is the most severe phenotype described in gene-related disease till date. This case report expands the clinical phenotype of gene related defects.
该基因编码THO复合物亚基2，它是转录输出（TREX）复合物的一个亚基，能特异性结合剪接信使核糖核酸（mRNA）以促进mRNA输出。已报道该基因的突变会导致12/35型X连锁智力迟钝综合征（XLMR - 12/35）（MIM编号：300957）。在此，我们首次描述了一个家族中两名男性胎儿出现的复发性先天性多发性关节挛缩症（AMC）表型。外显子组测序在该基因中鉴定出一种新的致病性变异，chrX: 122761817_122761820delTGAC（基因组组装GRCh37格式）或c.2482 - 1_2484delGTCA（根据Genbank转录本ID NM_001081550）。该变异影响内含子22和外显子23之间的共有剪接受体位点。这是迄今为止该基因相关疾病中所描述的最严重的表型。本病例报告扩展了该基因相关缺陷的临床表型。
