Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Periodontology, |
RCV001250387 | SCV001244922 | likely pathogenic | Ehlers-Danlos syndrome | 2020-04-25 | no assertion criteria provided | clinical testing | The p.Gly441Glufs*95 variant in COL3A1 has been reported in 1 Chinese families with autosomal dominant associated with severe periodontitis and tooth loss, clinical features suggested a provisional diagnosis of periodontal Ehlers-Danlos syndrome. Whole-exome sequencing identified missense mutation c.265T>C in C1R in all affected family members tested and the p.Gly441Glufs*95 variant in COL3A1 in the proband alone. the p.Gly441Glufs*95 variant in COL3A1 in the proband is a frameshift mutation resulting from a single base deletion, which may induce an error in the amino acid sequence from the base deletion site backward. This mutation may lead to a premature termination site after codon 95, encoding in termination of protein synthesis and a truncated protein. The truncated protein is generally degraded, resulting in reduced production of type III procollagen production in the affected individual. Mutations in COL3A1 are the only explanation for the vascular Ehlers-Danlos syndrome phenotypic spectrum, clinical features of the proband differed from those of his mother and maternal uncle in terms of (a) characteristic facial features; (b) thin and translucent skin with visible patterns on dorsum of feet; and (c) gingival fragility. In summary, the p.Gly441Glufs*95 variant in COL3A1 meets our criteria to be classified as pathogenic. |