A new form of familial platelet disorder caused by germline mutations in RUNX1 in a pedigree / 中华内科杂志

Objective: To investigate the clinical and biological characteristics of familial platelet disorder (FPD) with germline Runt-related transcription factor (RUNX) 1 mutations. Methods: Patients diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with RUNX1 mutations from February 2016 to December 2021 in Wuhan No.1 Hospital underwent pedigree analysis and were screened for gene mutations (somatic and germline). Patients diagnosed with FPD with germline RUNX1 mutations were enrolled and evaluated in terms of clinical characteristics and biological evolution. Bioinformatics analysis was used to assess the pathogenicity of mutations and to analyze the effect of mutated genes on the function of the corresponding protein. Results: Germline RUNX1 mutations were detected in three out of 34 patients suffering from MDS/AML who had RUNX1 mutations. A pedigree of FPD with RUNX1 (RUNX1-FPD) c.562A>C and RUNX1 c.1415T>C mutations was diagnosed, and the mutations were of patrilineal origin. Bioinformatics analysis indicated that the locus at positions 188 and 472 in the AML-1G type of RUNX1 was highly conserved across different species, and that variations might influence functions of the proteins. The mutations were evaluated to be highly pathogenic. Of the nine cases with germline RUNX1 mutations: two patients died due AML progression; one case with AML survived without leukemia after transplantation of hemopoietic stem cells; four patients showed mild-to-moderate thrombocytopenia; two cases had no thrombocytopenia. During the disease course of the proband and her son, mutations in RUNX1, NRAS and/or CEBPA and KIT appeared in succession, and expression of cluster of differentiation-7 on tumor cells was enhanced gradually. None of the gene mutations correlated with the tumor were detected in the four cases not suffering from MDS/AML, and they survived until the end of follow-up. Conclusions: RUNX1-FPD was rare. The mutations c.562A>C and c.1415T>C of RUNX1 could be the disease-causing genes for the family with RUNX1-FPD, and these mutations could promote malignant transformation. Biological monitoring should be carried out regularly to aid early intervention for family members with RUNX1-FPD.

Local hemostatic technic using a celluloid splint in bleeding disorders.

Controlling hemorrhage from dental treatment in bleeding disorder patients is one of the most serious procedures encountered by the dentist. In the Dental Division, Ramathibodi hospital, dentists use local hemostatic technics combined with replacement therapy, local hemostatic agents and antifibrinolytics in the management of bleeding disorders in dental patients, such as leukemia, ITP, hemophilia. Celluloid splints as an adjunct therapy is very beneficial in controlling hemorrhage in dental procedures as shown by 5 years experience with 278 patients. The advantages are: less expensive, lesser days hospitalized, better outcomes. Presently it is used as a routine technic in dental treatment.

Albinismo tirosinasa positivo asociado a transtorno de la agregación plaquetaria / Tyrosinase positive albinism associated with platelet aggregation disorders

Los autores estudian un caso de albinismo tirosinasa positivo con trastorno de la agregación plaquetaria. No se pudo comprobar la existencia de material ceroide en los macrófagos de la médula ósea. Pensamos, sin embargo que se trataba de una variente del síndrome de Hermansky-Pudlak, equiparable a un caso similar publicado en la literatura