Analysis of clinical manifestations, mutant gene and encoded protein in two Chinese MYH9-related disease families.

Abstract

BACKGROUND:

MYH9-related disease is a rare autosomal dominant disorder characterized by the triad of giant platelet, thrombocytopenia and inclusion bodies in neutrophil. In recent years, much progress has been made in the investigation of its clinical feature and pathogenesis.

METHODS:

Clinical manifestations were analyzed in two Chinese MYH9-related disease families. Polymerase chain reaction (PCR), DNA sequencing and CpoI restrictive endonuclease map analysis were used to identify spot mutation in nonmuscle myosin heavy chain 9 (MYH9) gene. Indirect immunofluence combined propidium iodine (PI) nuclei count-staining technology was applied to probe nonmuscle myosin heavy chain IIA (NMMHC-A) in MYH9-related disease neutrophils and platelets. Western blot was undergone to examine the expression of NMMHC-A in MYH9-related disease patients.

RESULTS:

All of the patients manifested with the typical triad, mild to moderate bleeding tendency were their common clinical feature, some patients were accompanied by renal lesion. G5521A mutation in MYH9 gene was identified in both families. Spindle-like inclusions with yellow fluorescence in MYH9-related disease neutrophils were clearly revealed by indirect immunofluence combined PI nuclei count-staining technology, which matched very well with the inclusions, detected by Wright-Giemsa's stain. An upregulation of NMMHC-A in MYH9-related disease neutrophils was observed by Western blotting analysis.

CONCLUSION:

Mutation of MYH9 gene exists in cases of Chinese MYH9-related disease. In the two families, the point mutation was located in exon 38(G5521A), and the transference rule of the MYH9 gene mutation is corresponding with clinical phenotype distribution. Indirect immunofluorescence combining with PI nuclei staining technology is sensitive and more specific than Wright-Giemsa's staining in detecting MYH9-related disease inclusions, with which we might easily distinguish MYH9-related disease inclusions from infection-associated inclusions. The expression of the NMMHC-A in MYH9-related disease neutrophils was upregulated than normal control.

• Authors: Yan Yi, Guang Sen Zhang, Min Xu, Zhu San Ling, Xiu Ru Shao, Jia Zeng Li, Jun Ma
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 373 Issue 1-2 Pg. 49-54 (Nov 2006) ISSN: 0009-8981 [Print] Netherlands
• PMID: 16806139 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

• Adult
• Blood Platelets (pathology)
• Blotting, Western
• China
• DNA Mutational Analysis
• Exons
• Family Health
• Female
• Humans
• Male
• Molecular Motor Proteins (genetics, metabolism)
• Myosin Heavy Chains (genetics, metabolism)
• Neutrophils (pathology)
• Pedigree
• Phenotype
• Point Mutation
• Polycystic Kidney, Autosomal Dominant (genetics, pathology)
• Polymerase Chain Reaction
• Sensitivity and Specificity
• Up-Regulation