Initiation codon mutation in βB1-crystallin (CRYBB1) associated with autosomal recessive nuclear pulverulent cataract

[摘要] Purpose: To identify the molecular basisfor autosomal recessively inherited congenital non-syndromicpulverulent cataracts in a consanguineous family with four affectedchildren. Methods: An autozygosity mappingstrategy using high density SNP microarrays and microsatellite markerswas employed to detect regions of homozygosity. Subsequently goodcandidate genes were screened for mutations by direct sequencing. Results: The SNP microarray datademonstrated a 24.96 Mb region of homozygosity at 22q11.21-22q13.2which was confirmed by microsatellite marker analysis. The candidatetarget region contained the β-crystallin gene cluster and directsequencing in affected family members revealed a novel mutation in CRYBB1(c.2T>A; p.Met1Lys). Conclusions: To our knowledge this isthe first case of an initiation codon mutation in a human crystallingene, and only the second report of a CRYBB1 mutationassociated with autosomal recessive congenital cataracts. In addition,although a number of genetic causes of autosomal dominant pulverulentcataracts have been identified (including CRYBB1) this is thefirst gene to have been implicated in autosomal recessive nuclearpulverulent cataract.

[学科分类] 生物化学/生物物理