Identification of the first duplication in MYH9-related disease: A hot spot for unequal crossing-over within exon 24 of the MYH9 gene

Daniela De Rocco, Nuria Pujol-Moix, Alessandro Pecci, Flavio Faletra, Valeria Bozzi, Carlo L. Balduini, Anna Savoia

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14 Citations (Scopus)

Abstract

MYH9-related disease (MYH9RD) is a rare autosomal dominant disorder caused by mutations in MYH9, the gene encoding the heavy chain of non-muscle myosin IIA. All patients present with congenital macrothrombocytopenia and inclusion bodies in neutrophils. Some of them can also develop sensorineural deafness, presenile cataracts, and/or progressive nephritis leading to end-stage renal failure. The spectrum of mutations so far identified is peculiar, consisting of mostly missense mutations. Others are nonsense and frameshift mutations, all localized in the COOH terminus of the protein, or in-frame deletions. We report a family with three affected members carrying a novel mutation, the first duplication (p.E1066_A1072dup), of MYH9. The mutation was localized within exon 24, where the presence of a 16 nucleotide repeat was likely to be responsible for unequal crossing-over. Of note, a deletion of the same amino acids 1066_1072 was also identified in another MHY9RD family. Since two of the four patients with the duplication or the deletion in exon 24 were affected with bilateral neonatal cataracts, we speculate that these mutations might correlate with the ocular defect, which is reported only in 16% of MYH9RD patients. © 2009 Elsevier Masson SAS. All rights reserved.
Original languageEnglish
Pages (from-to)191-194
JournalEuropean Journal of Medical Genetics
Volume52
Issue number4
DOIs
Publication statusPublished - 1 Jul 2009

Keywords

  • Duplication
  • Mutational screening
  • MYH9 gene
  • MYH9-related disease
  • Unequal crossing-over

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