title: First description of somatic mosaicism in MYH9 disorders.
abstract: MYH9 disorders are characterized by giant platelets, thrombocytopenia, and Dohle body-like cytoplasmic granulocyte inclusion bodies that result from mutations in MYH9, which encodes non-muscle myosin heavy chain-A (NMMHCA). These disorders are known to be transmitted in an autosomal dominant manner, although about 20% of cases are considered to be sporadic. We report here the first case of a MYH9 disorder because of somatic mosaicism. The patient was the father of a male with typical May-Hegglin anomaly. The father had normal platelet counts, however, both normal-sized and giant platelets were observed on his peripheral blood smears. In addition, 14% of neutrophils contained inclusion bodies and the rest showed a normal morphology. Quantitative fluorescent polymerase chain reaction analysis showed that only 6% of DNA from peripheral blood leucocytes harboured the mutation. The mosaicism was demonstrated at a similar rate in different tissues, buccal mucosa cells and hair bulb cells, implying that the mutation had occurred before gastrulation. Mosaicism might account for some de novo mutations in MYH9 disorders.
authors.affiliation: Department of Haemostasis and Thrombosis, Clinical Research Centre, National Hospital Organization Nagoya Medical Centre, Nagoya, Japan. kunishis@nnh.hosp.go.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Kunishima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Takao
authors.initials: T
authors.lastname: Yoshihara
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakase
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yokoi
authors.forename: Motohiro
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Saito
mesh_terms: D001483:Base Sequence; D001792:Blood Platelets / Q000473:pathology; D004252:DNA Mutational Analysis; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D007223:Infant; D008297:Male; D020409:Molecular Motor Proteins / Q000235:genetics*; D009030:Mosaicism; D018995:Myosin Heavy Chains / Q000235:genetics*; D009504:Neutrophils / Q000473:pathology; D013921:Thrombocytopenia / Q000097:blood / Q000235:genetics*
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains