A rare homozygous missense mutation of COL7A1 in a Vietnamese family

Abstract

We present a homozygous missense mutation in the COL7A1 gene (NM_000094.4: c.6262G>A, p.G2088R) in a case of inversa recessive dystrophic epidermolysis bullosa (RDEB-I) from a nonconsanguineous Vietnamese family. Although a heterozygous form of this mutation in combination with a premature termination codon allele has been shown to cause RDEB-I, this is the first report of homozygosity of this mutation as the etiology. Here, we investigated the molecular basis of the patient's disease for prenatal diagnosis after genetic counseling of the parents.

Fig. 1. Proband at the age of 4 and the pedigree analysis of the family in the study.

A–C Blisters and erosions on the trunk, palm creases, extremities and toes; D Family pedigree of the proband; E Multiple sequence alignment at amino acid position 2088 (highlighted in red); F Sanger sequencing results of the proband and his affected brother, healthy parents, and healthy brother.

Fig. 2. Immunofluorescence of rubbed skin samples from the proband’s forehead with corresponding healthy control samples.

Immunofluorescence staining was performed with antibodies against collagen IV, collagen VII, integrin α6, integrin β4, laminin γ2, and cytokeratin 5/6. White arrows indicate the fluorescence signals of these proteins. The proband (rubbed skin sample) had a homozygous variant, p.G2088R, which was predicted to be deleterious by in silico prediction tools. Regarding collagen VII, while the control showed a broad and clear signal, the proband showed low and interrupted signals, indicating a significant reduction in collagen VII. However, the collagen IV signal of the proband was similar to that of the control. The proband sample presented a slight reduction in laminin γ2 and integrin β4, which are indicators for the diagnosis of junctional EB. The signals of integrin α6 and cytokeratin 5/6, which are indicators for the diagnosis of basal EB simplex and junctional EB, were similar to those of controls.