Late onset and high-frequency dominant hearing loss in a family with MYH9 disorder

Abstract

MYH9 disorder is a rare autosomal-dominant disorder. We previously reported that it is caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9 disorder causes congenital macrothrombocytopenia accompanied by progressive sensorineural hearing loss, nephropathy, and cataract. However, there are few reports that describe the audiological features of MYH9 disorder. The objective of this study was to characterize auditory and other phenotypes of patients with MYH9 disorder. We examined nine subjects from one Japanese family. Audiological, ophthalmological, hematological, and imaging examinations were used to assess clinical features. We carried out genetic analysis of the causative gene, MYH9. Five subjects exhibited macrothrombocytopenia and neutrophil cytoplasmic inclusion bodies. Immunofluorescence analysis of neutrophil NMMHC-IIA revealed abnormal type II localization. Two subjects had high-frequency dominant hearing loss, which was adult onset and progressive. Only one subject had cataract. MYH9 sequencing analysis of all thrombocytopenic subjects revealed a heterozygous c.4270G>A mutation in exon 30 (p.D1424N). We identified five patients with MYH9 disorder from the family. The hearing impairment associated with MYH9 disorder in this family was characterized as adult onset, progressive, and high-frequency dominant. Hematological manifestations of MYH9 disorder show complete penetrance, whereas extra-hematological manifestations show incomplete penetrance and variable expressivity in this family.

MYH9 disorder: Identification and a novel mutation in patients with macrothrombocytopenia

“…Our findings regarding the age at which non‐HMs occur were consistent with previous research. Specifically, patients 1, 3, and 6 with non‐HMs had mutations in the head domain, especially p.R702C, which occurs in younger age groups, 16–20 as well as p.S96L and p.W33R 21–26 . Likewise, patients 8 and 9, who were older than patients 1, 3, and 6, had mutations in the tail domain (exon 30), in agreement with previous studies 3,17,21 .…”

“…Specifically, patients 1, 3, and 6 with non‐HMs had mutations in the head domain, especially p.R702C, which occurs in younger age groups, 16–20 as well as p.S96L and p.W33R 21–26 . Likewise, patients 8 and 9, who were older than patients 1, 3, and 6, had mutations in the tail domain (exon 30), in agreement with previous studies 3,17,21 . Patients 8 and 9, with p.F1446A mutation, had several typical symptoms of exon 30 (D1424N) mutations, namely, large MPD, high proportion of large platelets, and late onset of non‐HMs 17,27 …”

“…[21][22][23][24][25][26] Likewise, patients 8 and 9, who were older than patients 1, 3, and 6, had mutations in the tail domain (exon 30), in agreement with previous studies. 3,17,21…”

“…MYH9 disorder, a rare autosomal dominant disorder, is generally characterized by hematological manifestations (HMs) of macrothrombocytopenia and granulocyte Döhle body-like inclusion bodies (IB), 1,2 which may not be visible in peripheral blood smears (PBSs) of all patients. The MYH9 gene, encoding nonmuscle myosin heavy chain IIA (NMMHC-IIA), consists of motor (exons [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], neck (exon 20), and tail domains Abbreviations: HMs, hematological manifestations; IB, inclusion bodies; IFA, immunofluorescence analysis; IPF, immature platelet fraction ; ITP, immune thrombocytopenia; MPD, mean platelet diameter; MPV, mean platelet volume; NMMHC-IIA, non-muscle myosin heavy chain IIA; PBS, peripheral blood smear.…”

MYH9-related inherited thrombocytopenia

“…При выполнении аудиометрии характерное снижение слу-ха может выявляться уже в первые 10 лет жизни паци-ента и быстро прогрессировать с годами [6,7,16].…”