Novel single-base deletional mutation in major intrinsic protein (MIP) in autosomal dominant cataract.
OBJECTIVE
To further elucidate the cataract phenotype, and identify the gene and mutation for autosomal dominant cataract (ADC) in an American family of European descent (ADC2) by sequencing the major intrinsic protein gene (MIP), a candidate based on linkage to chromosome 12q13.


METHODS
Observational case series and laboratory experimental study.


METHODS
We examined two at-risk individuals in ADC2. We PCR-amplified and sequenced all four exons and all intron-exon boundaries of the MIP gene from genomic and cloned DNA in affected members to confirm one variant as the putative mutation.


RESULTS
We found a novel single deletion of nucleotide (nt) 3223 (within codon 235) in exon four, causing a frameshift that alters 41 of 45 subsequent amino acids and creates a premature stop codon.


CONCLUSIONS
We identified a novel single base pair deletion in the MIP gene and conclude that it is a pathogenic sequence alteration.
Geyer
David D
DD
Department of Ophthalmology, Rocky Mountain Lions Eye Institute, Denver, Colorado, USA.
Spence
M Anne
MA
Johannes
Meriam
M
Flodman
Pamela
P
Clancy
Kevin P
KP
Berry
Rebecca
R
Sparkes
Robert S
RS
Jonsen
Matthew D
MD
Isenberg
Sherwin J
SJ
Bateman
J Bronwyn
JB
D020346:Aquaporins / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics*
D020346:Aquaporins; D003062:Codon; D005136:Eye Proteins; D008562:Membrane Glycoproteins; C030328:aquaporin 0