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

Abstract

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.

• Authors: Daniela De Rocco, Barbara Zieger, Helen Platokouki, Paula G Heller, Annalisa Pastore, Roberta Bottega, Patrizia Noris, Serena Barozzi, Ana C Glembotsky, Helen Pergantou, Carlo L Balduini, Anna Savoia, Alessandro Pecci
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 56 Issue 1 Pg. 7-12 (Jan 2013) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 23123319 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Chemical References

• MYH9 protein, human
• Molecular Motor Proteins
• Myosin Heavy Chains

Topics

• Adolescent
• Adult
• Amino Acid Sequence
• Amino Acid Substitution
• Base Sequence
• Child
• Child, Preschool
• Exons
• Female
• Genes, Dominant
• Genetic Association Studies
• Humans
• Male
• Middle Aged
• Models, Molecular
• Molecular Motor Proteins (chemistry, genetics)
• Molecular Sequence Data
• Mutation
• Myosin Heavy Chains (chemistry, genetics)
• Pedigree
• Protein Conformation
• Sequence Alignment
• Syndrome
• Thrombocytopenia (diagnosis, genetics)
• Young Adult