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I. Perrault, S. Hanein, S. Gerber, J. Rozet, D. Ducroq, F. Barbet, A. Munnich, J. Dufier, J. Kaplan; Autosomal Dominant Inheritance in a Family Affected with a Genuine Form of Leber Congenital Amaurosis (LCA) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1492.
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Purpose: To identify the disease causing gene in a very unusual LCA family. The disease first occurred in a woman born to healthy first cousins who married an unrelated heathy man and yet had two children as severely affected as she. Patients and Methods: The family of interest is shown on the enclosed figure. The diagnosis of LCA was unambiguous in III2. In the first months of life she was found to carry the typical signs of the disease ie absence of ocular pursuit, searching nystagmus, oculo-digital signs of Franceschetti, and non recordable ERG. The profound visual deficiency remained stable throughout her life. This woman born to healthy first cousins (II2 and II3), hailing from an isolated region of Italy, married an unrelated man who never complained of any visual impairment. Yet, their two first children wher as severely affected as the mother and displayed all criteria required for the diagnosis of LCA. The screening of the seven already known LCA genes was undertaken by DHPLC and direct sequencing of genomic DNA. Results: In the patient III2, a heterozygous 1bp deletion was identified in the third exon of the CRX gene leading to a premature termination of the traduction. No other nucleotide change was found in the coding sequence of the CRX gene. This deletion segregated with the disease in the family ie was either absent in the mother II3, the paternal aunt II2, the healthy brother III3 or the healthy children IV3 and IV4. The deletion was also absent in the healthy husband III1. On the other hand, the six other LCA genes were screened for mutations under the hypothesis of a digenic inheritance. No mutation was found. Conclusions: Although the hypothesis of digenism cannot be completely ruled out, it is more probable that the disease is transmitted in this family as an autososmal dominant trait, accounted for by a heterozygous deletion in the CRX gene. View OriginalDownload SlideView OriginalDownload Slide
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