Background: To identify the underlying genetic defect responsible for microphthalmos eyes in two three-generation Chinese families.
Methods: In our study, we screened 425 potential eye disease-related genes of the proband of a three-generation Chinese family diagnosed with microphthalmos using next-generation sequencing-based target capture sequencing. Variants were filtered and analyzed to identify possible disease-causing variants before Sanger sequencing validation.
Results: We enrolled two families with microphthalmos (Family 1: microphthalmos with congenital ocular coloboma and Family 2: simple microphthalmos). Two novel heterozygous mutations, PXDN c.3165C>T (p.Pro1055Pro) and PXDN c.2640C>G (p.Arg880Arg), were found in Family 1, and CRYBB2 c.481G>A (p.Gly161Arg) was found in Family 2, but none of the mutations were found in the unaffected individuals, who were phenotypically normal. Multiple orthologous sequence alignment (MSA) revealed that the CRYBB2 p.Gly161Arg mutation was a deleterious effect mutation.
Conclusions: The three novel mutations found in our study extend our current understanding of the genetic basis of microphthalmos and provide early presymptomatic diagnosis and emphasize the significance of genetic diagnosis of microphthalmos.