To the Editor:

MYH9 syndrome represents a group of autosomal dominant macrothrombocytopenias caused by mutations in the MYH9 gene.1 Sensorineural deafness, cataracts, and/or progressive nephritis leading to endstage renal failure can be present.2, 3 Following a recent report demonstrating the expression of MYH9 protein in hepatic stellate cells,4 we studied the liver biochemistries and histology (two cases) of nine patients with MYH9 syndrome from seven unrelated families.Apart from the three related affected family members, no individuals shared the same MYH9 mutation.

Results of liver tests are shown in Table 1. Liver biopsies were available for two of the unrelated patients, a child and an adult (Patients 2 and 3). Histopathology revealed a normal lobular architectural pattern without abnormality of the reticulin framework and no evidence of nodular regenerative hyperplasia or noncirrhotic portal fibrosis (results not shown). In addition, viral serologies and detection of autoimmune hepatitis were negative in all.

Table 1. Results of Liver Tests
PatientAge/SexClinical FeaturesMYH9 MutationPlatelet Count G/LAST (N:15-35)ALT (N:15-40)ALP (N:40-115)GGT (N: 5-50)Total Bilirubin (N:<17 mmol/l)CPK (N: 20-200)Copper (N:10-22)PT % (N: > 70)Albumin g/l (N:37-53)Bile Acid (N: 0-5)
Patient 138/FNephritisG1214A754811222220057815103502
Patient 2*18/F C5797T414668409428100107546.91
Patient 3*53/MCataract, nephritisC3464T344756165291619018.285475
Patient 435/F delA 5998 59993057851104576612100424
Patient 512/FNephritisR702G69505568565950979305
Patient 652/MNephritisG4270A20435819426613.516312100513
Patient 713/M   4953975137781295482
Patient 818/M  53469538637101601083434
Patient 922/M T5767 + 2 T>A intron 3944428615027910013100502

To investigate the specificity of this association with MYH9 mutations, we also studied unaffected family members from three of these families and from 33 other patients with macrothrombocytopenias. These included Gray platelet syndrome (three patients), Bernard Soulier syndrome (three patients), Paris Trousseau Syndrome (four patients), idiopathic macrothrombocytopenia (13 patients), and autoimmune chronic macrothrombocytopenia (10 patients). None of these individuals had abnormal serum liver biochemistries.

The prevalence and clinical implications of these findings with regard to long-term hepatic function is unclear but it should be noted that the same findings have now been concurrently described by another group in another cohort of MYH9 syndrome patients.5 It should therefore be noted that while elevated transaminases were present even in our youngest patients, no evolution toward liver insufficiency has been identified. Given the expanding appreciation of MYH9 function in different cell types,6 it may therefore be of interest to examine the role of MYH9 genetic variation in individuals with abnormal liver-enzyme results but without other known etiologies.


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  • 1
    Seri L, Cusano R, Ganagraossa S, Caridi G, Bordo D, Lo Nigro C, et al. Mutation in MYH9 result in the May-Hegglin anomaly, and Fetchner and Sebastian syndromes. The May Hegglin/Fetchner Syndrome Consortium. Nat Genet 2000; 26: 103-105.
  • 2
    Balduini Cl, Pecci A, Savoia A. Recent advances in the understanding and management of MYH9 related inherited thrombocytopenia. Br J Haem 2011; 154: 161-174.
  • 3
    Bostrom MA, Freedman BI. The spectrum of MYH9 associated nephropathy. Clin J Am Soc Nephrol 2010; 5: 1107-1113
  • 4
    Liu Z, Van Rossen E, Timmermans JP, Geerts A, Van Grunsven LA, Reynaert H. Distinct roles for non muscle myosin II isoforms in mouse hepatic stellate cells. J Hepatol 2011; 54: 132-141.
  • 5
    Pecci A, Biino G, Fierro T, Bozzi V, Mezzasoma A, Noris P, et al. Alteration of liver enzymes is a feature of the Myh9-related disease syndrome. Plos One 2012; 7: 1-9.
  • 6
    Marigo V, Nigro A, Pecci A, Montanaro D, Di Stazio M, Balduini C, et al. Correlation between the clinical phenotype of MYH9 related disease and tissue distribution of class II non muscle myosin heavy chains. Genomics 2004; 83: 1125-1133.

Rémi Favier M.D.*, Analisa DiFeo Ph.D.†, Nathalie Hezard M.D., Ph.D.‡, Monique Fabre M.D.§, Pierre Bedossa M.D., Ph.D.¶, John A. Martignetti M.D., Ph.D.**, * Assistance Publique Hopitaux de Paris, Armand Trousseau Children's Hospital, French Reference Center for Inherited Platelet, Disorders and Inserm U1009, Villejuif, France, † Case Comprehensive Cancer Center, Case Western Reserve University 2103 Cornell Road, Wolstein Research Building, 2-127 Cleveland OH, USA, ‡ Laboratoire d'Hematologie, Hopital Robert Debre, CHU Reims, France, § Service d'anatomo Pathologie, Institut Gustave Roussy, 94805 Villejuif, France, ¶ Assistance Publique-Hopitaux de Paris, Departement de Pathologie, Hopital Beaujon, 92118 CLICHY, France, ** Departments of Genetics and Genomic Sciences and Pediatrics, Mount Sinai School of Medicine, 1425 Madison Ave., Box 1498, New York, NY 10029, USA.