Novel variants in PAX6 gene caused congenital aniridia in two Chinese families.
PurposeTo reveal the underlying genetic defect in two four-generation Chinese families with aniridia and explore the pathologic mechanism.MethodsFull ophthalmic examinations were performed in two families with aniridia. The PAX6 gene was directly sequenced in patients of two families, and the detected variants were screened in unaffected family members and two hundred unrelated healthy controls. Real-time quantitative PCR was used to explore pathologic mechanisms of the two variants.ResultsAniridia, cataract, and oscillatory nystagmus were observed in patients of the two families. In addition, we observed corneal opacity and microphthalmus in family 1, and strabismus, left ectopia lentis, microphthalmus, and microcornea in family 2. Sanger sequencing detected a novel 1-bp duplication (c.50dupA) in family 1 and a novel 2-bp splice site deletion (c.765+1_765+2delGT) in family 2. Sequencing of cDNA indicated skipping of exon 9 caused by the splice site deletion, being predicted to cause a premature stop codon, as well as the duplication. The PAX6 mRNA significantly lower in patients with aniridia than in unaffected family members in both families, suggesting that the duplication and splice site deletion caused nonsense-mediated mRNA decay.ConclusionsOur study identified two novel PAX6 variants in two families with aniridia and revealed the pathogenicity of the variants; this would expand the variant spectrum of PAX6 and help us better understand the molecular basis of aniridia, thus facilitating genetic counseling.
State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
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R
Zhang
State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
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S
Linpeng
State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
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X
Wei
State Key Laboratory of Medical Genetics, Central South University, Changsha, China.|Hunan Jiahui Genetics Hospital, Changsha, China.
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H
Li
State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
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Y
Huang
State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
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J
Guo
Hunan Jiahui Genetics Hospital, Changsha, China.
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Q
Wu
State Key Laboratory of Medical Genetics, Central South University, Changsha, China.|Hunan Jiahui Genetics Hospital, Changsha, China.
D
D
Liang
State Key Laboratory of Medical Genetics, Central South University, Changsha, China.|Hunan Jiahui Genetics Hospital, Changsha, China.
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L
Wu
D000293:Adolescent; D000328:Adult; D015783:Aniridia / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000071841:PAX6 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D012313:RNA