Abstract | PURPOSE: METHODS: A four-generation family with an affected female, and a history of congenital blindness and hearing loss, was identified through the pro-band. A second family, with a full-term female infant, was evaluated through ophthalmic examinations and found to exhibit ocular features, such as retinal folds, retinal detachment and peripheral exudates. Peripheral blood specimens were collected from several affected and unaffected family members. DNA was extracted and analyzed by single-strand conformation polymorphism (SSCP) following polymerase chain reaction (PCR) amplification of the exons of the Norrie disease gene. The amplified products were sequenced by the dideoxy chain termination method. RESULTS: In an X-linked four-generation family, a novel missense (A118D) mutation in the third exon of the Norrie disease gene, was identified. The mutation was transmitted through three generations and cosegregated with the disease. The affected maternal grandmother and the unaffected mother carried the same mutation in one of their alleles. In an unrelated sporadic family, a heterozygous missense mutation (C96Y) was identified in the third exon of the Norrie disease gene in an affected individual. Analysis of exon-1 and 2 of the Norrie disease gene did not reveal any additional sequence alterations in these families. The mutations were not detected in the unaffected family members and the 116 normal unrelated controls, suggesting that they are likely to be the pathogenic mutations. CONCLUSIONS: The results further strengthen the proposal that X-linked disorders can occur in female carriers, due likely to an unfavorable X-inactivation.
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Authors | B S Shastry, M Hiraoka, D C Trese, M T Trese |
Journal | European journal of ophthalmology
(Eur J Ophthalmol)
1999 Jul-Sep
Vol. 9
Issue 3
Pg. 238-42
ISSN: 1120-6721 [Print] United States |
PMID | 10544980
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Topics |
- Blindness
(congenital, genetics)
- Dosage Compensation, Genetic
- Female
- Genetic Linkage
- Heterozygote
- Humans
- Male
- Retina
(abnormalities)
- Retinal Diseases
(genetics)
- Sequence Analysis, DNA
- Vitreous Body
(abnormalities)
- X Chromosome
(genetics)
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