RESUMEN
ANKRD26-related thrombocytopenia (ANKRD26-RT or THC2, MIM 188 000), an autosomal dominant thrombocytopenia, is unresponsive to immunosuppressive therapy and susceptible to hematological malignancies. A large number of pediatric patients are diagnosed with immune thrombocytopenia (ITP) every year; however, thrombocytopenia of genetic origin is often missed. Extensive characterization of ANKRD26-RT will help prevent missed diagnosis and misdiagnosis. Furthermore, identification of ANKRD26-RT will help in the formulation of an accurate diagnosis and a treatment plan. In our study, we report cases of two Chinese pediatric patients with ANKRD26-RT and analyze their clinical characteristics, gene mutations, and treatment modalities. Both patients were 1-year-old and presented with mild bleeding (World Health Organization(WHO) score grade 1), different degrees of platelet reduction, normal mean platelet volume, and megakaryocyte maturation impairment not obvious. Genetic tests revealed that both patients had ANKRD26 gene mutations.Patient 1 had a mutation c.-140C>G of the 5' untranslated region (UTR), and patient 2 had a mutation of c.-127A>T of 5'UTR. Both patients were treated with eltrombopag, and the treatment was no response, with no adverse reactions.
What is the background? ANKRD26-RT is an autosomal dominant thrombocytopenia which is unresponsive to immunosuppressive therapy and susceptible to hematological malignancies.It is rare and lacks specific clinical features, making misdiagnosis easy.Some studies report that eltrombopag is safe and effective for short-term treatment of the disease; however, these reports are limited.What we did and summary of findings. We retrospectively studied the clinical manifestations and diagnosis process of ANKRD26-RT and discussed the treatment efficacy of immunosuppressants and eltrombopag for its management.We found two pediatric cases of patients with ANKRD26-RT with varying degrees of thrombocytopenia, mild bleeding, normal mean platelet volume, and megakaryocyte maturation impairment that was not obvious. Immunosuppressant treatment wasunresponsiveor temporarily responsivebut not sustained , and short-term administration of eltrombopag (25 mg/day) was safe, but it did not effectively improve the patients' platelet counts.What is the impact? If patients clinically diagnosed with immune thrombocytopenia do not respond to immunosuppressive agents, genetic testing should be conducted to exclude hereditary thrombocytopenia, and a normal mean platelet volume should not exclude the possibility of the disease.For patients with ANKRD26-RT, eltrombopag is safe for short-term use;however, 25 mg/day treatment is unresponsive.Ourreport complements data on the diagnosis and management of ANKRD26-RT disease in children.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Trombocitopenia , Humanos , Lactante , Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Péptidos y Proteínas de Señalización Intercelular/genética , Mutación , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/genética , Púrpura Trombocitopénica Idiopática/terapia , Trombocitopenia/etiología , Trombocitopenia/genética , Resultado del TratamientoRESUMEN
Wiskott-Aldrich syndrome (WAS) also called the eczema-thrombocytopenia-immunodeficiency syndrome is a primary immunodeficiency disease with X-linked recessive inheritance caused by mutations in the WAS protein (WASp) gene and characterized by thrombocytopenia with reduced platelet volume, eczema, immunodeficiency, and increased risk of malignant tumours. The mutations will lead to separate WAS severity which can be typical severe 'classical' WAS or less severe 'non-classical' WAS. This article will review and analyse clinical and immune characteristics of five unrelated Chinese families harbouring classical and non-classical WAS. The expression of WASp was detected in the peripheral blood monocytes (PBMC) by flow cytometry, and five mutations were found by WAS gene sequencing, one of which had not been reported in the literature, namely frameshift mutation c.1240_1247delCCACTCCC (p. P414Sfs*41).
Asunto(s)
Leucocitos Mononucleares/metabolismo , Mutación/genética , Proteína del Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/inmunología , China , Análisis Mutacional de ADN , Eccema , Familia , Femenino , Humanos , Lactante , Leucocitos Mononucleares/inmunología , Masculino , Volúmen Plaquetario Medio , Trombocitopenia , Síndrome de Wiskott-Aldrich/genéticaRESUMEN
Congenital factor VII deficiency (FVIID) is a rare F7 gene mutation causing bleeding disorder inherited in an autosomal recessive manner. In this study, we aimed to identify genetic defects and analyze their relationships with phenotype in three Chinese FVIID patients. The diagnosis of FVIID was made based on FVII coagulant activity (FVII:C) levels assessed through prothrombin time assay. Direct sequencing and protein modeling were performed to detect genetic mutations and the resulting protein expression. Patient 1, a 2-year-old girl, presented with mild bleeding and was found to have a FVII:C of 0.2% and a compound heterozygous F7 Cys389Gly/Cys115Arg mutation. Patient 2, a 7-year-old boy, consulted for moderate bleeding and was found to have a FVII:C of 0.8% and a compound heterozygous F7 Thr241Asn/Pro324Leu mutation. Patient 3, a 5-year-old boy who developed a mild bleeding after trauma was found to have a FVII:C of 1.8% and a compound heterozygous F7 Thr241Asn/ IVS5-2A>G mutation. We hereby report three congenital FVIID patients with FVII:C less than 2% and their respective F7 mutations, two of which (F7 Cys115Arg, Pro324Leu) are novel. The molecular model analysis of the two novel mutations F7 Cys115Arg and Pro324Leu respectively indicated impairment of the proper folding of epidermal growth factor 1 domain situated on F7 gene and impairment of the procoagulant function of FVII both leading to the congenital deficiency of FVII.
Asunto(s)
Deficiencia del Factor VII/genética , Factor VII/genética , Niño , Preescolar , Factor VII/química , Deficiencia del Factor VII/congénito , Femenino , Humanos , Masculino , Modelos Moleculares , Mutación , Mutación Puntual , Conformación ProteicaRESUMEN
ß-Thalassemia (ß-thal), one of the most common form of single-gene inheritable blood diseases in the world, is highly prevalent in southern China, especially in the Guangxi Zhuang Autonomous Region. To update the ß-thal mutation spectrum in this region, we performed hematological and genetic analyses on 888 ß-thal major (ß-TM), ß-thal intermedia (ß-TI) and ß-thal carrier patients, aged 0-15 years old, from different parts of Guangxi Province. We identified 55 genotypes and 18 ß-thal mutations. The codons 41/42 (-TTCT) (HBB: c.126_129delCTTT) (43.97%), codon 17 (A>T) (HBB: c.52A>T) (25.43%), -28(A>G) (HBB: c.-78A>G) (8.18%), IVS-II-654 (C>T) (HBB: c.316-197C>T) (7.85%) and codon 26 (G>A) (HBB: c.79G>A) (5.02%) were the five most common, accounting for more than 90.0%. The results of our study are providing an up-to-date ß-thal mutation spectrum in the 0-15-year-old pediatric population, which will help genetic counseling and prevention of ß-TM in mainland China's most endemic region, Guangxi Zhuang Autonomous Region.
Asunto(s)
Talasemia beta , Adolescente , Niño , Preescolar , China/epidemiología , Codón , Frecuencia de los Genes , Genotipo , Humanos , Lactante , Recién Nacido , Mutación , Globinas beta/genética , Talasemia beta/epidemiología , Talasemia beta/genéticaRESUMEN
Glanzmann thrombasthenia (GT) is an inherited disorder of platelet aggregation resulting from quantitative and/or qualitative abnormalities of the glycoprotein IIb/IIIa complex. We analyzed the expression of GPIIb/IIIa and the gene sequencing in two pedigrees with GT, so as to determine the type and the relationship between genotype and clinical phenotype. Platelet aggregation tests and flow cytometric studies were performed, along with gene sequencing. Both probands were classified as grade III of bleeding. Platelet aggregation was absent or defective upon stimulation with physiological stimuli like AA and ADP, but platelets agglutinated normally in response to ristocetin. MFI values were considerably reduced. Gene sequencing showed ITGB3 mutations p.Cys549Ser/p.Leu705CysfsTer4 in proband 1 and p.Cys549Ser/p.Gln254Lys in proband 2 and her sister. This study reports one novel ITGB3 mutant gene, p.Gln254Lys, of which we will explore the potential pathogenicity.