Identification of Novel Copy Number Variations of VCAN Gene in Three Chinese Families with Wagner Disease

Abstract

The VCAN/versican gene encodes an important component of the extracellular matrix, the chondroitin sulfate proteoglycan 2 (CSPG2/versican). Heterozygous variants targeting exon 8 of VCAN have been shown to cause Wagner disease, a rare autosomal dominant non-syndromic vitreoretinopathy that induces retinal detachment, cataracts and permanent visual loss. In this study, we report on six patients from three unrelated families with Wagner disease in whom we identified three novel copy number variations of VCAN. Quantitative real-time polymerase chain reaction analysis identified deletions, including one exon–intron boundary of exon 8 or both exons 8 and 9, causing the haploinsufficiency of VCAN mRNAs.

A novel splicing variant of VCAN identified in a Chinese family initially diagnosed with familial exudative vitreoretinopathy

“…The reverse‐transcribed reaction included an initial step at 42°C for 15 min, followed by 95°C for 3 min. The cDNA was amplified with the four specific pairs of primers for the four known transcript isoforms of the VCAN described previously (Li, Li, Sun, et al, 2020 ). GAPDH primers were used as a control.…”

“…At present, 34 VCAN variants have been reported based on the Human Gene Variant Database (HGMD) Professional 2021.4 and 18 of them cause WVR. The 18 variants included 12 different splice variants and six gross deletions (Ankala et al, 2018 ; Araújo et al, 2018 ; Brézin et al, 2011 ; Burin‐des‐Roziers et al, 2017 ; Chen et al, 2013 ; Jewsbury et al, 2014 ; Klee et al, 2021 ; Kloeckener‐Gruissem et al, 2006 , 2013 ; Li, Li, Sun, et al, 2020 ; Li, Li, Yang, et al, 2020 ; Meredith et al, 2007 ; Miyamoto et al, 2005 ; Mukhopadhyay et al, 2006 ; Ronan et al, 2009 ; Rothschild, Audo, et al, 2013 ; Rothschild, Brézin, et al, 2013 ). All the splicing effect variants have been located in the conserved exon 8 splice site (Ankala et al, 2018 ; Brézin et al, 2011 ; Chen et al, 2013 ; Jewsbury et al, 2014 ; Kloeckener‐Gruissem et al, 2006 , 2013 ; Meredith et al, 2007 ; Miyamoto et al, 2005 ; Mukhopadhyay et al, 2006 ; Ronan et al, 2009 ; Rothschild, Audo, et al, 2013 ; Rothschild, Brézin, et al, 2013 ), while the six gross deletions all involved exon 8 (Ankala et al, 2018 ; Burin‐des‐Roziers et al, 2017 ; Li, Li, Sun, et al, 2020 ).…”