Three Novel Mutations of Microphthalmos Identified in Two Chinese Families

Genetic alterations are a major cause of microphthalmos, while novel-related genes and mutations in microphthalmos have rarely been explored. To identify the underlying genetic defect responsible for microphthalmos eyes in two three-generation Chinese families, we screened 425 genes involved in common inherited non-syndromic eye diseases with next-generation sequencing-based target capture sequencing of the two probands of two three-generation Chinese families diagnosed with microphthalmos. Variants were filtered and analyzed to identify possible disease-causing variants before Sanger sequencing validation. We enrolled two families with microphthalmos (Family 1: microphthalmos with congenital ocular coloboma and Family 2: simple microphthalmos). Two novel heterozygous mutations, Peroxidasin (PXDN) c.3165C>T (p.Pro1055Pro) and PXDN c.2640C>G (p.Arg880Arg), were found in Family 1, and Crystallin Beta B2 (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. In conclusion, the three novel mutations found in our study extend our current understanding of the genetic basis of microphthalmos and provide early pre-symptomatic diagnosis and emphasize the significance of genetic diagnosis of microphthalmos.