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.