Molecular genetic diagnosis by next-generation sequencing in a cohort of Mexican patients with haemophilia and report of novel variants

• Published in: Blood cells, molecules, & diseases molecules, & diseases, 2020-07, Vol.83, p.102423-102423, Article 102423
• Main Authors: Villarreal-Martínez, Laura, Ibarra-Ramirez, Marisol, Calvo-Anguiano, Geovana, Lugo-Trampe, José de Jesús, Luna-Záizar, Hilda, Martínez-de-Villarreal, Laura Elia, Meléndez-Aranda, Lennon, Jaloma-Cruz, Ana-Rebeca
• Format: Article
• Language: English
• Subjects: Coagulation panel; Cohort Studies; F8 and F9 variants; Factor VIII - chemistry; Factor VIII - genetics; FVIII inhibitor; Genetic Predisposition to Disease; Genotype-phenotype correlation; Haemophilia A and B; Hemophilia A - diagnosis; Hemophilia A - epidemiology; Hemophilia A - genetics; Hemophilia B - diagnosis; Hemophilia B - epidemiology; Hemophilia B - genetics; High-Throughput Nucleotide Sequencing; Humans; Mexico - epidemiology; Models, Molecular; Mutation; Next-generation sequencing
• ISSN: 1079-9796; 1096-0961
• DOI: 10.1016/j.bcmd.2020.102423

Molecular analysis in haemophilia is currently used in the diagnosis, treatment and prognosis of this disease. Hispanic populations in Latin America have been of interest to researchers due to the reportedly high prevalence of inhibitors in these patients. To perform next-generation sequencing (NGS) in a cohort of Mexican patients with HA and HB and correlate with clinical phenotypes. Patients with Haemophilia A (HA) or haemophilia B (HB), were evaluated using NGS with an Ion AmpliSeq Custom Panel. Odds ratios (ORs) for associations between F8 variants and inhibitors were obtained. A total of 85 patients (60 with HA and 25 with HB) were included. Pathogenic variants in F8 were found in 93.3% of HA patients and in F9 in 96% of HB patients. Twelve novel potentially pathogenic variants were found. Inhibitors were observed in 20% of patients with severe HA. Four patients clinically diagnosed with HA were negative for F8 variants. Overall detection rate of pathogenic variants in F8 and F9 genes was 94.6%. We identified 12 non previously reported variants and pathogenic variants in other coagulation related genes. Molecular diagnosis of HA and HB permits better options for management, assessment and genetic counseling.