OBJECTIVE: To analyze clinical features and genetic cause for a Chinese pedigree affected with microphthalmia. METHODS: The proband and his parents were subjected to whole exome sequencing (WES) to identify potential pathogenic variants. Sanger sequencing was carried out to confirm the result of WES in available members from the pedigree. Prenatal diagnosis was provided to the proband's mother by genetic testing of amnionic DNA. RESULTS: A heterozygous nonsense mutation c.289C>T (p.R97*) was identified in the OTX2 gene among three patients from the pedigree by WES. The result was confirmed by Sanger sequencing. The proband's mother has carried the same mutation but did not have microphthalmia. The proband's father, aunt and the mother's fetus did not carry the mutation. CONCLUSION The c.289C>T (p.R97*) mutation probably underlies the microphthalmia in this pedigree. Above result has facilitated genetic counseling and prenatal diagnosis.
China ; Female ; Humans ; Male ; Microphthalmos/genetics* ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with microphthalmia. METHODS: Clinical data of the proband was collected. Whole exome sequencing (WES) was carried out to screen potential pathogenic variants in the proband. Candidate variant was verified by Sanger sequencing of the proband and his family members. Pathogenicity of the variant was predicted by searching the PubMed database and bioinformatic analysis. Sanger sequencing of amniotic fluid sample was carried out for prenatal diagnosis. RESULTS: The proband and his father were found to harbor a heterozygous c.151C>G (p.R51G) variant of the MAB21L2 gene. The same variant was not found in his mother and grandparents. Based on the guidelines of American College of Medical Genetics, the c.151C>G (p.R51G) variant was predicted as likely pathogenic. CONCLUSION The c.151C>G (p.R51G) variant of the MAB21L2 gene probably underlay the microphthalmia in the proband. Above finding has facilitated prenatal diagnosis for this pedigree.
China ; Coloboma ; Eye Proteins ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; Microphthalmos/genetics* ; Mutation ; Osteochondrodysplasias ; Pedigree ; Pregnancy ; Prenatal Diagnosis