TY - JOUR
T1 - Identification of the first duplication in MYH9-related disease
T2 - A hot spot for unequal crossing-over within exon 24 of the MYH9 gene
AU - De Rocco, Daniela
AU - Pujol-Moix, Nuria
AU - Pecci, Alessandro
AU - Faletra, Flavio
AU - Bozzi, Valeria
AU - Balduini, Carlo L.
AU - Savoia, Anna
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
KW - Duplication
KW - Mutational screening
KW - MYH9 gene
KW - MYH9-related disease
KW - Unequal crossing-over
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U2 - 10.1016/j.ejmg.2009.01.006
DO - 10.1016/j.ejmg.2009.01.006
M3 - Article
C2 - 19450438
AN - SCOPUS:67650600638
VL - 52
SP - 191
EP - 194
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
SN - 1769-7212
IS - 4
ER -