Potential conflict of interest: Nothing to report.
A new feature of the MYH9-related syndrome: Chronic transaminase elevation†
Article first published online: 27 NOV 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 57, Issue 3, pages 1288–1289, March 2013
How to Cite
Favier, R., DiFeo, A., Hezard, N., Fabre, M., Bedossa, P. and Martignetti, J. A. (2013), A new feature of the MYH9-related syndrome: Chronic transaminase elevation. Hepatology, 57: 1288–1289. doi: 10.1002/hep.25913
- Issue published online: 28 FEB 2013
- Article first published online: 27 NOV 2012
- Accepted manuscript online: 17 JUL 2012 12:00AM EST
- Manuscript Accepted: 11 JUN 2012
- Manuscript Revised: 3 JUN 2012
- Manuscript Received: 19 APR 2012
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.
|Patient||Age/Sex||Clinical Features||MYH9 Mutation||Platelet Count G/L||AST (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 3*||53/M||Cataract, nephritis||C3464T||34||47||56||165||29||16||190||18.2||85||47||5|
|Patient 4||35/F||delA 5998 5999||30||57||85||110||45||7||66||12||100||42||4|
|Patient 9||22/M||T5767 + 2 T>A intron 39||44||42||86||150||27||9||100||13||100||50||2|
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.
- 1Mutation 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., , , , , , et al.
- 2Recent advances in the understanding and management of MYH9 related inherited thrombocytopenia. Br J Haem 2011; 154: 161-174., , .
- 3The spectrum of MYH9 associated nephropathy. Clin J Am Soc Nephrol 2010; 5: 1107-1113, .
- 4Distinct roles for non muscle myosin II isoforms in mouse hepatic stellate cells. J Hepatol 2011; 54: 132-141., , , , , .
- 5Alteration of liver enzymes is a feature of the Myh9-related disease syndrome. Plos One 2012; 7: 1-9., , , , , , et al.
- 6Correlation between the clinical phenotype of MYH9 related disease and tissue distribution of class II non muscle myosin heavy chains. Genomics 2004; 83: 1125-1133., , , , , , et al.
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.