Monoallelic missense variants in cause a novel autosomal dominant microphthalmia.

PURPOSE

The biallelic variant of has previously been documented in conjunction with the autosomal recessive cerebellar, ocular, craniofacial, and genital syndrome (COFG). The purpose of this study was to investigate the gene-disease association of and the newly discovered autosomal dominant (AD) microphthalmia.

METHODS

We report the presence of an exceptionally rare missense variant in a single allele of the Arg51 codon of among four individuals from a single family diagnosed with microphthalmia, which suggesting an autosomal dominant inheritance pattern. Subsequently, based on comprehensive literature review, we identified another 13 families that have reported cases of autosomal dominant microphthalmos.

RESULTS

Genotype-phenotype analysis revealed that patients with a single allele missense variant in exhibited solely eye abnormalities. This starkly diverged from the clinical presentation of COFG, typified by the concurrent occurrence of ocular and extraocular symptoms stemming from the biallelic variant in . Our findings revealed that the heterozygous pathogenic variant in resulted in the emergence of autosomal dominant microphthalmia. By combining these genetic and experimental evidence, the clinical validity of and the emerging autosomal dominant microphthalmia can be regarded as moderate.

CONCLUSION

In summary, there is sufficient convincing evidence to prove that is a novel pathogenic gene responsible for autosomal dominant microphthalmia, thus offering valuable insights for precise diagnosis and targeted therapeutic interventions in cases of microphthalmia.