MYH9 related disease: four novel mutations of the tail domain of myosin-9 correlating with a mild clinical phenotype.
MYH9-related disease (MYH9-RD) 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 congenital macrothrombocytopenia and inclusion bodies in neutrophils. Some of them can also develop sensorineural deafness, presenile cataract, and/or progressive nephropathy leading to end-stage renal failure. We report four families, each with a novel mutation: two missense mutations, in exons 31 and 32, and two out of frame deletions in exon 40. They were associated with no bleeding diathesis, normal, or only slightly reduced platelet count and no extra-hematological manifestations, confirming that alterations of the tail domain cause a mild form of MYH9-RD with no clinically relevant defects.
Pecci
Alessandro
A
Department of Internal Medicine, University of Pavia and IRCCS Policlinico San Matteo Foundation, Pavia.
Panza
Emanuele
E
De Rocco
Daniela
D
Pujol-Moix
Nuria
N
Girotto
Giorgia
G
Podda
Luigi
L
Paparo
Carmelo
C
Bozzi
Valeria
V
Pastore
Annalisa
A
Balduini
Carlo L
CL
Seri
Marco
M
Savoia
Anna
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D030342:Genetic Diseases, Inborn / Q000097:blood / Q000235:genetics*; D006402:Hematologic Diseases / Q000097:blood / Q000235:genetics*; D006801:Humans; D045586:Intranuclear Inclusion Bodies; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics*; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D009504:Neutrophils
C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains