Identification of a novel CRYBB2 missense mutation causing congenital autosomal dominant cataract.
OBJECTIVE
To identify the genetic defect in a four-generation Croatian family presenting with autosomal dominant cataract.


METHODS
Genome-wide linkage analysis with 250K single nucleotide polymorphism (SNP) arrays was performed using DNA from one unaffected and seven affected individuals. Mutation screening of candidate genes was performed by bidirectional Sanger sequencing.


RESULTS
Evidence for linkage was observed for eight genomic regions. Among these was a locus on chromosome 22 which encompasses the β-crystallin gene cluster. This cluster includes four genes, namely beta-crystallin B1 (CRYBB1), beta-crystallin B2 (CRYBB2), beta-crystallin B3 (CRYBB3), and beta-crystallin A4 (CRYBA4). A novel sequence variant was found in the CRYBB2 gene (p.Arg188His). This variant cosegregated with the disease phenotype in all affected individuals but was not present in the unaffected family members and 100 healthy control subjects.


CONCLUSIONS
We report a novel missense mutation, p.Arg188His, in CRYBB2 associated with congenital cataract in a family of Croatian origin. This variant is the most COOH-terminal missense mutation in CRYBB2 that has been identified so far.
Centre for Ophthalmology, Institute for Ophthalmic Research, Molecular Genetics Laboratory, Tuebingen, Germany. nicole.weisschuh@unituebingen.de
Nicole
N
Weisschuh
Sabine
S
Aisenbrey
Bernd
B
Wissinger
Angelika
A
Riess
D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D017523:Croatia / Q000208:ethnology; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D038205:beta-Crystallin A Chain / Q000235:genetics; D038206:beta-Crystallin B Chain / Q000235:genetics*
C103907:CRYBA4 protein, human; C105601:CRYBB1 protein, human; C103908:CRYBB3 protein, human; D038205:beta-Crystallin A Chain; D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2