title: Identification of the first duplication in MYH9-related disease: a hot spot for unequal crossing-over within exon 24 of the MYH9 gene.
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.
authors.affiliation: Medical Genetics, Department of Reproductive and Developmental Sciences, Institute for Maternal and Child Health-IRCCS Burlo Garofolo, University of Trieste, Via dell'Istria 65/1, 34137 Trieste, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: De Rocco
authors.forename: Nuria
authors.initials: N
authors.lastname: Pujol-Moix
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Flavio
authors.initials: F
authors.lastname: Faletra
authors.forename: Valeria
authors.initials: V
authors.lastname: Bozzi
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Balduini
authors.forename: Anna
authors.initials: A
authors.lastname: Savoia
mesh_terms: D000328:Adult; D001483:Base Sequence; D001792:Blood Platelets / Q000648:ultrastructure; D002386:Cataract / Q000235:genetics*; D003434:Crossing Over, Genetic; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000648:ultrastructure; D005091:Exons; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D020440:Gene Duplication; D005799:Genes, Dominant; D006801:Humans; D002479:Inclusion Bodies / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains