Eight single genes have been implicated as causative for ADC to
date each in a single family with the exception of the
βA1-crystallin, gap junction protein α-3(
connexin46),
γD-crystallin, PAX6, and the
β-crystallin gene (
CRYBB2) all of which have
been reported in two. A chain termination mutation in the
β-crystallin gene (
CRYBB2) on chromosome
22,
36 37 a missense mutation in the
gap junction
protein α-8 gene (
connexin50; MP70)
38 on
1q21.1,
39 and a missense mutation in the human
αA-crystallin gene (
CRYAA)
40 on
chromosome 21 have been shown to cause ADC. Activation of the
γE-crystallin pseudogene
(
CRYGEP1)
41 on 2q33-q35 was reported as
the basis of the Coppock-like cataract. Recently, Heon and
colleagues
42 restudied the family and found that the
variation in the pseudogene
CRYGEP1, presumed to activate
the gene, is a polymorphism and identified a missense mutation in a
highly conserved region of exon 2 of the
γC-crystallin
(CRYGC). Kannabiran and colleagues
43 44 demonstrated
a mutation of a donor splice junction (intron C) of the
βA1-crystallin gene on 17q11.2-q12 as the basis for the
ADC in an Indian family
45 ; we studied a large Brazilian
family with ADC of variable morphology and found a new and different
mutation at the same
βA1-crystallin splice site (Bateman
et al., unpublished data, 2000). Two-point mutations, a missense and a
frame-shift, in
gap junction protein α-3 (
connexin46) on chromosome 13q11-12 have been reported in
two families with granular opacities of the fetal nucleus and juvenile
cortex.
46 Two families with missense mutations of the
γD crystallin (CRYGD) gene (2q33-q35) and disparate
clinical features have been reported.
42 47 Although
mutations in the
homeobox DNA-binding PAX6 gene usually
cause aniridia and/or anterior segment dysgenesis, isolated cataracts
have been documented.
48 49 Hyperferritinemia, an autosomal
dominant systemic disease characterized by elevated serum ferritin,
congenital cataracts, and abnormal liver biopsy,
50 is
caused by mutations of the
iron responsive element of ferritin
L-subunit gene
51 and may represent an additional
locus.