Novel Consensus Splice Site Pathogenic Variation in THOC2 Gene Leads to Recurrent Arthrogryposis Multiplex Congenita Phenotype: A Case Report.

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.