Nonpenetrance of the most frequent autosomal recessive leber congenital amaurosis mutation in NMNAT1

Anna M Siemiatkowska, Janneke H M Schuurs-Hoeijmakers, Danielle G M Bosch, F Nienke Boonstra, Frans C C Riemslag, Mariken Ruiter, Bert B A de Vries, Anneke I den Hollander, Rob W J Collin, Frans P M Cremers

    Onderzoeksoutput: Bijdrage aan tijdschriftArtikelOnderzoekpeer review

    Samenvatting

    IMPORTANCE: The NMNAT1 gene was recently found to be mutated in a subset of patients with Leber congenital amaurosis and macular atrophy. The most prevalent NMNAT1 variant was p.Glu257Lys, which was observed in 38 of 106 alleles (35.8%). On the basis of functional assays, it was deemed a severe variant.

    OBSERVATIONS: The p.Glu257Lys variant was 80-fold less frequent in a homozygous state in patients with Leber congenital amaurosis than predicted based on its heterozygosity frequency in the European American population. Moreover, we identified this variant in a homozygous state in a patient with no ocular abnormalities.

    CONCLUSIONS AND RELEVANCE: On the basis of these results, the p.Glu257Lys variant is considered not fully penetrant. Homozygotes of the p.Glu257Lys variant in most persons are therefore not associated with ocular disease. Consequently, genetic counselors should exercise great caution in the interpretation of this variant.

    Originele taal-2Engels
    Pagina's (van-tot)1002-4
    Aantal pagina's3
    TijdschriftJAMA Ophthalmology
    Volume132
    Nummer van het tijdschrift8
    DOI's
    StatusGepubliceerd - aug 2014

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