Novel compound heterozygous variant of GJA8 gene in two siblings with congenital cataract mimics an autosomal recessive trait

Background GJA8 gene is known to cause autosomal dominant congenital cataract. Here we report a novel compound heterozygous variant of GJA8 gene in two siblings that mimics an autosomal recessive trait. Patients and methods Two siblings from a non-consanguineous Chinese family suffered from isolated congenital cataract. Whole exome sequencing was performed to identify disease-causing variants followed by a confirmatory Sanger sequencing. Results Whole exome sequencing revealed a novel compound heterozygous variant of GJA8 gene, c.855delG(p.Met286Trpfs*71)/c.1125delC(p.Gly376Glufs*33), in the proband. Sanger sequencing confirmed that the proband and his sister harboured this compound heterozygous variant, while the parents were heterozygous carriers, suggesting an autosomal recessive inheritance pattern. Both parents showed mildly impaired vision, but only the father had mild nuclear opacities, suggesting an autosomal dominant trait with reduced penetrance in one of the pathogenic alleles. Conclusions Our report shows compound heterozygous variant of GJA8 gene may mimic autosomal recessive inheritance pattern, and reminds clinicians to perform needful examination. The two novel pathogenic GJA8 variants expand the mutational spectrum of congenital cataract. This study also provides accurate genetic diagnosis for the family.