Cataract 5, Multiple Types

A number sign (#) is used with this entry because of evidence that multiple types of cataract are caused by heterozygous mutation in the gene that encodes heat-shock transcription factor-4 (HSF4; 602438) on chromosome 16q22.

Description

Congenital cataracts cause 10 to 30% of all blindness in children, with one-third of cases estimated to have a genetic cause (summary by Bu et al., 2002). Mutations in the HSF4 gene have been found to cause multiple types of cataract, which have been described as infantile, lamellar, zonular, nuclear, anterior polar, stellate, and Marner-type.

The preferred title for this entry was formerly 'Lamellar Cataract,' with 'Cataract, Marner Type; CAM; CTM' an included title.

Clinical Features

Striking pedigrees segregating cataract were reported by Cridland (1918), Hilbert (1912), Jankiewicz and Freeberg (1956), Keizer (1952), Knapp (1926), and Marner (1949), among others. In the Dutch family reported by Marner (1949), 132 individuals in 8 generations were affected, mainly by zonular cataract but some by nuclear, anterior polar, or stellate cataract. The opacities were progressive, and 'anticipation' (progressively earlier onset in successive generations) was suggested. Marner et al. (1989) provided a follow-up on this family.

Bu et al. (2002) reported affected members of a large Chinese family with lamellar cataract described as a perinuclear-shaped lens opacity with a transparent embryonic nucleus. The earliest age of observed onset was 15 months.

Mapping

Maumenee (1979) studied a family in which 10 members over 3 generations had posterior polar cataracts with progressive lens opacity leading to surgery at ages varying from the first year of life to 39 years. The pedigree showed father-to-son transmission. Linkage analysis revealed no crossover between haptoglobin (140100) markers on chromosome 16q22 and posterior polar cataract, and a lod score of 1.8 (theta = 0.0) was obtained.

Richards et al. (1984) examined 21 affected and 39 unaffected family members from a kindred in which posterior polar cataract segregated as an autosomal dominant trait. A maximum lod score of 2.109 (theta = 0.1) was obtained between haptoglobin and cataract in this family.

Eiberg et al. (1988) studied the large Danish family with cataract originally reported by Marner (1949) and found strong evidence of linkage to haptoglobin (140100) on chromosome 16; lod score = 8.33 at theta = 0.05 for males and females combined. See also Marner et al. (1989).

Bu et al. (2002) carried out whole-genome linkage analysis of a Chinese family with lamellar cataract and found that the disorder was associated with inheritance of a 5.11-cM region on chromosome 16.

Inheritance

The transmission pattern of cataract in the family reported by Marner (1949) was consistent with autosomal dominant inheritance.

Molecular Genetics

Bu et al. (2002) identified a missense mutation in the HSF4 gene (602438.0002) in affected members of the Danish family with cataract reported by Marner (1949) and studied by Eiberg et al. (1988). They also identified mutations in the HSF4 gene (602438.0001; 602438.0003-602438.0004) in affected members of a large Chinese family with lamellar cataract.

Animal Model

Hejtmancik (1998) tabulated 8 animal models of cataract in which molecular defects had been identified.

History

In a family with cataract reported by Harman (1910), malformation of the fingers was associated.