Progressive sutural cataract associated with a BFSP2 mutation in a Chinese family.
OBJECTIVE
To identify the mutation underlying the segregation of progressive sutural congenital cataracts in a four-generation Chinese pedigree.


METHODS
Genomic DNA was extracted from the peripheral blood samples of members of the pedigree. A genome-wide scan was performed using microsatellite markers spaced at about 10 cM intervals. Linkage analysis was carried out using a Linkage software package. Ten additional microsatellite markers for the positive region were selected for precise targeting, and haplotype data were processed using Cyrillic software to define the region of the disease gene. Mutation detection was carried out by sequencing candidate genes.


RESULTS
Significant evidence of linkage was obtained at marker D3S1279 (LOD score [Z] =2.32, recombination fraction [theta]=0.0). Precise targeting and haplotype analysis traced the disease gene to a 38.6 cM region bounded by D3S1267 and D3S1614 at 3q21.1- q26.2 near BFSP2, which encodes a lens-specific beaded filament protein. Sequencing results revealed a 3-bp deletion of nucleotides 696-698 (GAA) in exon 3 of BFSP2, which is predicted to cause an in-frame deletion of glutamic acid residue 233 from the polypeptide encoded by the mutant gene. This deletion was seen neither in any unaffected member of the family nor in 50 unrelated control individuals.


CONCLUSIONS
We observed progressive isolated sutural cataract associated with a deletion mutation of the BFSP2 gene in a Chinese pedigree. It highlights the physiological importance of the beaded filament protein and supports the role of BFSP2 in human cataract formation.
Zhang
Lu
L
Eye hospital, The First Affiliated Hospital, Harbin Medical University, Harbin, China. hljzhanglu@gmail.com <hljzhanglu@gmail.com>
Gao
Linghan
L
Li
Zhijian
Z
Qin
Wei
W
Gao
Weiqi
W
Cui
Xiaobo
X
Feng
Guoyin
G
Fu
Songbin
S
He
Lin
L
Liu
Ping
P
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000235:genetics* / Q000473:pathology*; D002648:Child; D018450:Disease Progression; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D008040:Genetic Linkage; D018698:Glutamic Acid; D006239:Haplotypes; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree
D005136:Eye Proteins; D007381:Intermediate Filament Proteins; C084808:phakinin; D018698:Glutamic Acid