Novel Exon 7 Deletions in TSPAN12 in a Three-Generation FEVR Family: A Case Report and Literature Review

Abstract

Familial exudative vitreoretinopathy (FEVR) is a severe clinically and genetically heterogeneous disease that is characterized by vascular disorder. FEVR exhibits strikingly variable clinical phenotypes, ranging from asymptomatic to total blindness. In this case, we present a patient who was first treated as having high myopia and retinopathy but was finally diagnosed with FEVR caused by the heterozygous deletion of exon 7 in TSPAN12 with the aid of whole genome sequencing (WGS). Typical vascular changes, including vascular leakage and an avascular zone in the peripheral retina, were observed in the proband using fundus fluorescein angiography (FFA), and the macular dragging was shown to be progressing in the follow-up visit. Furthermore, the proband showed unreported TSPAN12-related phenotypes of FEVR: ERG (full-field electroretinogram) abnormalities and retinoschisis. Only mild vascular changes were exhibited in the FFA for the other three family members who carried the same deletion of exon 7 in TSPAN12. This case expands our understanding of the phenotype resulting from TSPAN12 mutations and signifies the importance of combining both clinical and molecular analysis approaches to establish a complete diagnosis.

Familial Exudative Vitreoretinopathy: A Case Report

“…It is phenotypically variable and at times it is an incidental diagnosis or may present with complete loss of vision. 5 FEVR has different inheritance patterns depending on the gene involved. Inheritance is Autosomal Dominant and rarely XLR or AR, with high penetrance and variable expressivity.…”

De novel heterozygous copy number deletion on 7q31.31-7q31.32 involving TSPAN12 gene with familial exudative vitreoretinopathy in a Chinese family

“…Therefore, when analyzing phenotypes, it is essential not to neglect the role of each gene contained in the CNVs. Mutations in the TSPAN12 gene have been found to count for 5.6% to 8.0% of FEVR patients and are common (12.8%) in patients with asymptomatic mild FEVR [25] . A total of 12 FEVR patients with CNVs involving the TSPAN12 gene have been reported so far (Table 4) [16,[25][26][27] , with 4 out of 12 cases showing a complete deletion of the entire TSPAN12 gene.…”

“…Mutations in the TSPAN12 gene have been found to count for 5.6% to 8.0% of FEVR patients and are common (12.8%) in patients with asymptomatic mild FEVR [25] . A total of 12 FEVR patients with CNVs involving the TSPAN12 gene have been reported so far (Table 4) [16,[25][26][27] , with 4 out of 12 cases showing a complete deletion of the entire TSPAN12 gene. Among these cases, there was only one affected individual who exhibited additional symptoms such as cleft lip, lowset dysmorphic ears, and died at the age of 20mo, along with FEVR.…”