[Analysis of two Chinese pedigrees affected with Alport syndrome due to novel variants of COL4A5 gene].

OBJECTIVE

To explore the genetic basis for two Chinese pedigrees affected with Alport syndrome.

METHODS

Potential variants of the COL4A5 gene were screened by next generation sequencing (NGS). Candidate variants were verified by Sanger sequencing of other members from the pedigrees as well as 100 healthy controls. ClustalX 2.1 win was used to analyze the conservation of amino acid sequences. SWISS-MODEL was used for assessing the influence of variations on the protein structure.

RESULTS

Two heterozygous missense variants of the COL4A5 gene, namely c.2210G>A (p.Gly737Asp) and c.3799G>A (p.Gly1267Ser), were respectively identified in the affected individuals from the two pedigrees but not among the 100 healthy controls. Neither variant was reported previously.

CONCLUSION

The c.2210G>A (p.Gly737Asp) and c.3799G>A (p.Gly1267Ser) variants of the COL4A5 gene probably underlay the Alport syndrome in these pedigrees. Above finding has enriched the spectrum of COL4A5 gene variants and provided a basis for genetic counseling and prenatal diagnosis for the families.