MYH9-related disease: five novel mutations expanding the spectrum of causative mutations and confirming genotype/phenotype correlations

DE ROCCO DANIELA; ZIEGER BARBARA; PLATOKOUKI HELEN; HELLER PAULA G; PASTORE ANNALISA; BOTTEGA ROBERTA; NORIS PATRIZIA; BAROZZI SERENA; GLEMBOTSKY ANA C; PERGANTOU HELEN; BALDUINI CARLO L; SAVOIA ANNA; PECCI ALESSANDRO

EUROPEAN JOURNAL OF MEDICAL GENETICS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2012 p. 1 - 18

1769-7212

MYH9-related disease (MYH9-RD)is a rare autosomal dominant syndromic disorder caused by mutations in MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (myosin 9). MYH9-RD is characterized by congenital macrothrombocytopenia and typical inclusion bodies in neutrophils associated with a variable risk of developing sensorineural deafness, presenile cataract, and/or progressive nephropathy. The spectrum of mutations responsible for MYH9-RD is limited. We report five families, each with a novel MYH9 mutation. Two mutations, p.Val134Gly and p.Arg702Ser, affect the motor domain of myosin-9, whereas the other three, p,Met847_Glu853dup, p.Lys1048_Glu1054del, and p.Asp1447Tyr, hit the coiled-coil tail domain of the protein. The motor domain mutations were associated with more severe clinical phenotypes than those in the tail domain.