Molecular diagnosis of a family with May-Hegglin anomaly / 中华医学遗传学杂志

Objective@#To explore the molecular basis for a pedigree affected with May-Hegglin anomaly (MHA).@*Methods@#Peripheral blood samples were collected and subjected to DNA extraction. Exons 1, 10, 16, 24, 25, 26, 30, 31, 33, 38 and 40 and flanking sequences of the MYH9 gene were subjected to PCR amplification and Sanger sequencing. Changes in protein expression were determined by an indirect immunofluorescence assay. Platelet aggregation function of the proband was assessed by thromboelastogram.@*Results@#The proband and his second son both carried a heterozygous 5521G>A (GAG→AAG) missense variant in exon 38 of the MYH9 gene, leading to p. Glu1841Lys substitution at position 1841 of amino acid sequence. Immunofluorescence showed inclusions containing NMMHC-ⅡA. Thromboelastogram suggested enhanced platelet aggregation function of the proband.@*Conclusion@#The c. 5521G>A variant of MYH9 gene has co-segregated with the phenotype of MHA in this pedigree. To assess the aggregation function of platelet by thromboelastogram can predict the risk of bleeding in MHA patients.

A Case of Myosin-heavy-chain-9 (MYH9) Gene Mutation Confirmed May-Hegglin Anomaly: 11-year Follow-up / 임상소아혈액종양

May-Hegglin anomaly (MHA) is a myosin-heavy-chain-9 (MYH9)-related disorder characterized by thrombocytopenia with giant platelets and inclusion bodies in leukocytes. MHA does not require treatment, but it may be misdiagnosed as immune thrombocytopenic purpura (ITP) and inappropriately managed. Reported herein is a case of a 12 year old female patient diagnosed as MHA with laboratory findings of severe thrombocytopenia and giant platelets in peripheral blood morphology, and followed up until 23 years of age. The patient had been diagnosed with ITP and treated with intravenous gamma-globulin therapy at another hospital, and showed no improvements in platelet count. She was then referred to our hospital for further diagnostic workup and followed up for 11 years, showing platelet count of 6,000-20,000/µL and prolonged platelet function test. She was occasionally treated with iron therapy due to iron-deficiency anemia. In 2014, we conducted a DNA analysis that revealed c.4339G>T(p.Asp1447Tyr), a known mutation of MYH9 gene.

A Case of Myosin-heavy-chain-9 (MYH9) Gene Mutation Confirmed May-Hegglin Anomaly: 11-year Follow-up / 임상소아혈액종양

May-Hegglin anomaly (MHA) is a myosin-heavy-chain-9 (MYH9)-related disorder characterized by thrombocytopenia with giant platelets and inclusion bodies in leukocytes. MHA does not require treatment, but it may be misdiagnosed as immune thrombocytopenic purpura (ITP) and inappropriately managed. Reported herein is a case of a 12 year old female patient diagnosed as MHA with laboratory findings of severe thrombocytopenia and giant platelets in peripheral blood morphology, and followed up until 23 years of age. The patient had been diagnosed with ITP and treated with intravenous gamma-globulin therapy at another hospital, and showed no improvements in platelet count. She was then referred to our hospital for further diagnostic workup and followed up for 11 years, showing platelet count of 6,000-20,000/µL and prolonged platelet function test. She was occasionally treated with iron therapy due to iron-deficiency anemia. In 2014, we conducted a DNA analysis that revealed c.4339G>T(p.Asp1447Tyr), a known mutation of MYH9 gene.

Morphology Observation of A Family of May-Hegglin Abnormal Cell / 现代检验医学杂志

Objective The morphological changes were observed in a pedigree with May-Hegglin anomaly cells.Methods Blood routine detection of abnormal May-Hegglin family members,peripheral blood cell Wright-Giemsa staining,and obser-vation of the white blood cell and platelet morphology.Made bone marrow smears of the proband,and megakaryocyte counts and classification.The proband peripheral blood leukocyte TEM examination were collected and analyzed by PCR sequen-cing.Results To reduce the May-Hegglin abnormal family blood platelet count in different degree,peripheral blood eosino-phil,eosinophilic inclusion visible form was not an alkaline cells,monocytes,neutrophils in body.Conclusion It’s provided valuable clues to diagnosis of morphological examination for May-Hegglin disorders.

May-Hegglin Anomaly Diagnosed by Genetic Study in a Newborn Infant / 대한주산의학회잡지

May-Hegglin anomaly is an autosomal dominant platelet disorder characterized by giant platelets, thrombocytopenia, and Dohle-like cytoplasmic inclusion bodies in granulocyte. Usually, diagnosis was delayed because they do not have life-threatening bleeding. We experienced a case of May-Hegglin anomaly, which was diagnosed with genetic study at neonate. A 3 days old female has bilateral cephalhematoma at birth after a Caesarean section delivery. Thrombocytopenia with inclusion bodies in granulocyte was observed at peripheral blood cell morphology. Her mother had thrombocytopenia at pregnancy and was diagnosed May-Hegglin anomaly through MYH9 mutation gene study. Accordingly, infant had genetic study and found same gene mutation with mother. Based on the family history, we can diagnose May-Hegglin anomaly in a newborn infant who has cephalhematoma and thrombocytopenia by genetic study.

A Trp33Arg Mutation at Exon 1 of the MYH9 Gene in a Korean Patient with May-Hegglin Anomaly

In this report, we describe a Korean patient with May-Hegglin anomaly from a mutation of the MYH9 gene. The proband was a 21-year-old man with thrombocytopenia. He did not have a bleeding tendency. His neutrophil count was normal at 7490/mm3; however, the neutrophils contained abnormal basophilic inclusions in their cytoplasm. The platelet count was decreased at 15000/mm3 with giant platelets. Coagulation test results were not remarkable. Direct sequencing of MYH9 revealed that he was heterozygous for a mutation in exon 1, which was a 97T>A substitution mutation affecting codon 33, substituting tryptophan with arginine (Trp33Arg). Family study showed that both of his parents had normal phenotype and genotypes, indicating a de novo occurrence of the mutation in the proband.

A Nonsense C5797T (R1933X) Mutation of MYH9 Gene in a Family with May-Hegglin Anomaly / 대한혈액학회지

May-Hegglin anomaly (MHA) is an autosomal dominant disorder characterized by macrothrombocytopenia and leukocyte inclusions. In 1992, we reported the first Korean case of MHA family. Again, in this family, we identified a nonsense C5797T mutation (R1933X) in the MYH9 gene, encoding non-muscle myosin heavy chain A. To the best of our knowledge, our genetic study in this MHA family is the first report of mutation resulting in the truncation of 28 of 34 amino acids of the carboxy-terminal tailpiece of the myosin heavy chain in Korea.