Cataract 33, Multiple Types

A number sign (#) is used with this entry because of evidence that multiple types of cataract (CTRCT33) are caused by heterozygous or homozygous mutation in the beaded filament structural protein-1 gene (BFSP1; 603307) on chromosome 20p12.

Description

Mutations in the BFSP1 gene have been found to cause multiple types of cataract, which have been described as cortical, nuclear, and progressive punctate lamellar. Both autosomal dominant and autosomal recessive modes of inheritance have been reported.

Clinical Features

Ramachandran et al. (2007) examined 11 affected and 8 unaffected members of a large consanguineous Indian family (family 30023) segregating autosomal recessive juvenile-onset cortical cataract. Cataract was first documented at 5 years of age in all affected individuals but 1, in whom it was noted at 2 years of age. Examination of 3 individuals who had not yet undergone surgery revealed fluffy, cotton-like cortical opacities with occasional grape-like cysts in the anterior cortex. Corneal diameter and axial length were normal, and no other eye abnormalities were detected.

Wang et al. (2013) reported a 5-generation Chinese family in which 15 members had autosomal dominant bilateral nuclear cataract. Opacities were visible in childhood. None of those affected had other ocular or systemic defects.

Zhai et al. (2017) reported a 4-generation Han Chinese family segregating isolated progressive punctate lamellar cataract.

Mapping

Ramachandran et al. (2007) performed a genomewide scan with 382 microsatellite markers in a large consanguineous Indian family segregating autosomal recessive developmental cataract and found linkage to a 9.3-cM (5.43-Mb) region on chromosome 20p between markers D20S852 and D20S912, with a maximum 2-point lod score of 5.4 obtained at D20S860.

Inheritance

The transmission pattern of juvenile-onset cortical cataract in the family reported by Ramachandran et al. (2007) was consistent with autosomal recessive inheritance.

The transmission pattern of cataract in the Chinese families reported by Wang et al. (2013) and Zhai et al. (2017) was consistent with autosomal dominant inheritance.

Molecular Genetics

Autosomal Recessive Inheritance

In 11 affected and 8 unaffected members of a large consanguineous Indian family with juvenile-onset cortical cataract mapping to chromosome 20p, Ramachandran et al. (2007) sequenced the BFSP1 gene and identified homozygosity for a 3,343-bp deletion (603307.0001) in affected individuals. Unaffected carriers were heterozygous for the change, which was not found in 100 ethnically matched chromosomes.

By next-generation sequencing of 32 cataract-associated genes in 46 apparently nonsyndromic congenital cataract probands, Ma et al. (2016) identified compound heterozygous mutations in the BFSP1 gene (c.1492del, S498LfsX24; c.812T-C, I271T; NM_001195.4) in a consanguineous family (family 46) with cataract and microcornea. The unaffected mother was heterozygous for the frameshift mutation, confirming that these mutations were in trans. The proband's affected brother and his father were not available for study.

Autosomal Dominant Inheritance

In a 5-generation Chinese family in which 15 members had autosomal dominant nuclear cataract unlinked to known cataract loci, Wang et al. (2013) performed whole-exome sequencing and identified heterozygosity for a missense mutation (D348N; 603307.0002) in the BFSP1 gene. The mutation was confirmed by Sanger sequencing and segregated with cataract in the family. It was not found in 200 control individuals.

By targeted next-generation sequencing of 54 cataract-associated genes in 27 Han Chinese families with cataract, Zhai et al. (2017) identified a heterozygous splice site mutation in the BFSP1 gene (603307.0003) in a 4-generation family (family 19) segregating progressive punctate lamellar cataract. The mutation segregated with cataract in all family members available for testing and was not found in 100 control individuals.