A novel de novo duplication mutation of PAX6 in a Chinese family with aniridia and other ocular abnormalities.
Aniridia is a congenital panocular disorder caused by the mutations of the paired box gene-6 (PAX6). To investigate the clinical characterization and the underlying genetic defect in a Chinese family with aniridia and other ocular abnormalities, we recruited the family members who underwent ophthalmic examination. Two patients in this family, the proband and his affected son, both have bilateral aniridia, foveal hypoplasia and nystagmus. Moreover, the proband also had presenile cataracts, but his affected son did not show cataracts at the time of examination. Sequencing PAX6 revealed that a heterozygous duplication mutation c.95_105dup11, predicted to generate non-functional truncated protein at position Gly36 (p.G36X), was found in the affected individuals but not in any of the unaffected family members including the parents of the proband. Haplotype analysis showed that the proband and his affected son shared a common disease-related haplotype, which was arisen from the proband's unaffected father through crossing-over. In conclusion, we identified a novel de novo duplication mutation of PAX6 in the aniridia and other ocular abnormalities family. This mutation has occurred de novo on a paternal chromosome by direct duplication, which presumably results from replication slippage or unequal non-sister chromatids exchange during spermatogenesis.
1] Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China [2] Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China [3].
Jianfu
J
Zhuang
1] Biomedical Engineering Center, Fujian Medical University, Fuzhou, Fujian, China [2].
Xiaole
X
Chen
Biomedical Engineering Center, Fujian Medical University, Fuzhou, Fujian, China.
Zhihua
Z
Tan
Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
Yihua
Y
Zhu
Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China.
Kanxing
K
Zhao
Biomedical Engineering Center, Fujian Medical University, Fuzhou, Fujian, China.
Juhua
J
Yang
D000293:Adolescent; D000328:Adult; D015783:Aniridia / Q000175:diagnosis / Q000235:genetics*; D044466:Asian People; D002681:China; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D020440:Gene Duplication; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins