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

DE ROCCO D.; ZIEGER B; PLATOKOUKI H; HELLER PG.; PASTORE A.; BOTTEGA R; NORIS P; BAROZZI S; GLEMBOTSKY AC.; PERGANTOU H; BALDUINI CL.; SAVOIA A.; PECCI A.

EUROPEAN JOURNAL OF MEDICAL GENETICS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2013 vol. 56 p. 7 - 12

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.Val34Gly 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