Patients present congenital macrothrombocytopenia and inclusions of NMMHC-IIA in leukocytes, and have a variable risk of developing kidney damage, sensorineural deafness, presenile cataracts and/or liver enzymes abnormalities.
The objective of this study was to investigate the severity and propensity for progression of SNHL in a large series of MYH9-RD patients in relation to the causative NMMHC-IIA mutations.
One of the MYH9 mutations, p.R705H, was previously reported to be associated with DFNA17, an autosomal dominant non-syndromic sensorineural hearing loss without any other features associated.
MYH9-RD is characterized by congenital macrothrombocytopenia and typical inclusion bodies in neutrophils associated with a variable risk of developing sensorineural deafness, presenile cataract, and/or progressive nephropathy.
MYH9-related disorders: report on a patient of Greek origin presenting with macroscopic hematuria and presenile cataract, caused by an R1165C mutation.
Previously, MYH9 missense mutations have been shown to cause the autosomal-dominant MYH9 (ADM9) spectrum, characterized by large platelets, leukocyte Döhle bodies, and, variably, sensorineural deafness, cataracts, and glomerulopathy.
We conclude that mutations in MYH9 are infrequently found in patients with nonsyndromic deafness and suggest that MYH9 mutations infrequently cause isolated sensorineural hearing loss.
This argument is relevant not only to cell physiology, but also to human pathology since mutations of the MYH9 gene encoding non-muscle myosin heavy chain II A (NMMHC-A) cause MYH9-related disease (MYH9-RD), an autosomal dominant disorder characterized by platelet macrocytosis, thrombocytopenia and leukocyte inclusions, variably associated with sensorineural hearing loss, cataracts and/or glomerulonephritis.
Nonsyndromic autosomal-dominant, adult-onset sensorineural hearing loss resulting from DFNA17 was described in a single American kindred in 1997, and the causative gene was subsequently identified as MYH9.
Thus, our results suggest that mutations in MYH9 result in three megakaryocyte/platelet/leukocyte syndromes and are important in the pathogenesis of sensorineural deafness, cataracts and nephritis.