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The GJA8 allele encoding CX50I247M is a rare polymorphism, not a cataract-causing mutation
Jochen Graw1, Werner Schmidt, Peter J Minogue
1Helmholtz Center Munich - German Research Center for Environmental Health, Institute of Developmental Genetics, D-85764 Neuherberg, Germany.
Molecular Vision
|September 17, 2009
Summary
A connexin50 (CX50) variant was studied in a child with congenital cataracts. Genetic, cellular, and physiological data suggest this variant is a rare, silent polymorphic allele, not disease-causing.
Area of Science:
- Ophthalmology
- Genetics
- Cell Biology
Background:
- Congenital cataracts can be linked to genetic mutations affecting lens proteins.
- Connexin50 (CX50) is a key protein in lens fiber cell communication, crucial for maintaining lens transparency.
Purpose of the Study:
- To genetically, cellularly, and physiologically characterize a connexin50 (CX50) variant found in a child with congenital cataracts.
- To determine if the identified CX50 variant is responsible for the observed cataracts.
Main Methods:
- Collected lens and blood samples for genetic analysis (sequencing, restriction digestion).
- Utilized immunofluorescence in HeLa cells to study connexin protein distribution.
- Assessed functional channel formation using two-microelectrode voltage-clamp in Xenopus oocytes.
Main Results:
- The proband exhibited bilateral cataracts, while parents were unaffected.
- A G>T transition in the GJA8 gene resulted in a methionine to isoleucine substitution at position 247 of CX50 (CX50I247M).
- This variant was present in the unaffected mother, and both wild-type CX50 and CX50I247M formed gap junction plaques and induced currents in oocytes.
Conclusions:
- The CX50I247M substitution, previously linked to cataracts, is likely a rare, silent polymorphic variant.
- The genetic, cellular, and electrophysiological data do not support this variant as the cause of congenital cataracts.
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