Mutations in the MYH9 gene are responsible for a group of related thrombocytopenias: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome, based on the morphologic aspects of Döhle-like bodies and the combination of different clinical findings at the time of diagnosis. These disorders are characterized by mild to severe thrombocytopenia with large-sized platelets. The typical clinical manifestation is macrothrombocytopenia; however, the bleeding tendency is usually moderate. Thrombocytopenia ranges from mild to severe and remains stable in an individual throughout their lifetime. Other clinical features may include high tone deafness, cataracts, leukocyte inclusions, and kidney disease leading in some cases to renal failure.
gene encodes the nonmuscle myosin heavy chain, class IIA. To date, 43 different mutations of the MYH9
gene in more than 200 families have been identified.5-7
Most causative MYH9
mutations reported to date have been missense, although in-frame deletions of a few amino acids, as well as nonsense and frameshift mutations have also been reported.8,9
Some of the reported mutations have occurred de novo
as with our case. The proportion of cases caused by de novo
mutations is 20-38%.10
In Korea, until recently, seven families of MHA have been identified.11-18
Of them, mutation analysis was performed in only two families and revealed previously reported mutations.17,18
In this report, we described a patient with MHA due to a missense mutation in the MYH9
gene. The mutation was a T-to-A substitution in exon 1 of MYH9
(c.97T>A), replacing tryptophan of the codon 33 with arginine (p.Trp33Arg) on the head domain of NMMHC-IIA. Two cases of Trp33Arg have also recently been reported in patients with MHA, as abstracts,5,6
and this is the third report in the world of this mutation and the first in Asia, to the best of our knowledge. Until now, 43 mutations in 14 different exons have been described.5-7,16,19-24
Exons 1-19 encode for the head and neck domains of NMMHC-IIA , while exons 20-40 encode the tail portion of the protein.7
Exon 1, 16, 26, 30 and 40 are relatively frequent sites of mutations. The mutation in our patient occurred on the actin binding site of the head domain of NMMHC-IIA at exon 1.
Previous studies reported that patients with a mutation in exon 1 of MYH9
had a high frequency of hearing or renal impairment ().5-7,17,19-24
The patient in the present report showed no evidence of hearing or renal impairment. However, further monitoring is needed for the possible development of these complications.
Table 1 Mutations and Clinical Features in MYH9-Related Thrombocytopenia 5-7,16,19-24