A novel de novo MYH9 mutation in MYH9-related disease: A case report and review of literature

Abstract

Introduction: MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in MYH9, which is responsible for encoding nonmuscle myosin heavy chains IIA (NMMHCIIA). MYH9-RD is clinically characterized by congenital macrothrombocytopenia, granulocyte inclusions variably associated with the risk of developing progressive sensorineural deafness, cataracts and nephropathy.

Patient concerns: A 5-year-old boy had a history of a mild bleeding tendency and chronic thrombocytopenia, first identified at four months of age. No other family members were noted to have similar clinical features or hematologic disorders.

Diagnoses: The boy was diagnosed with MYH9-RD. Light microscopic examination of peripheral blood films (Wright-Giemsa stain) showed marked platelet macrocytosis with giant platelets and basophilic Döhle-like inclusions in 83% of the neutrophils. Immunofluorescence analysis disclosed a type II pattern, manifested by neutrophils which contained several circle-to-oval shaped cytoplasmic NMMMHCA-positive granules. Sequencing analysis of MYH9-RD genes was carried out and revealed a novel missense mutation of c.97T>G (p.W33G) in the patient but not in his parents.

Intervention: No treatment is necessary. Recognition of MYH9-RD is important to Avoiding unnecessary and potentially harmful treatments.

Outcomes: The patient's condition remained stable during the follow-up.

Conclusions: As a result of identifying this missense mutation in this particular case, we have added c.97T>G (p.W33G) to the broad spectrum of potential MYH9 mutations.

Figure 1

Platelet and neutrophil morphology (original magnification ×1000). (A) Light micrograph of Wright–Giemsa-stained peripheral blood. Typical large inclusion body in a neutrophil is indicated by an arrowhead. (B) Light micrograph of Wright–Giemsa-stained peripheral blood. A giant platelet as large as erythrocyte and a cytoplasmic inclusion body in a neutrophil were observed. (C) Immunofluorescence localization of myosin-9 in neutrophil granulocyte. Normal myosin-9 distribution pattern is shown for comparison. (D) An immunofluorescence micrograph of a neutrophil immunostained with anti-NMMHCIIA localization.

Figure 2

The results of direct sequencing of MYH9 exon 2 in the proband and family numbers. The proband was heterozygous for a missense mutation of c.97T>G (p.W33G). His parents did not have the mutation, indicating a de novo occurrence of the mutation in the proband.