Molecular characterization of hemophilia B patients in Colombia

Abstract

BackgroundHemophilia B (HB) is a coagulation disorder with an X‐linked recessive inheritance pattern, caused by plasma FIX deficiency. In Colombia, HB is considered a rare and high‐cost disease, with 362 males reported in 2017.MethodsHere, we characterized 20 HB apparently unrelated families by PCR amplification and Sanger sequencing.ResultsFourteen unique variants were identified: seven missense, three nonsense, one variant in the 3′ UTR region, two large deletions >50 bp, and one intronic substitution that affects splicing c.520+13A>G that was present in 7/20 patients (35%). All these variants have been previously reported in the literature, except for exons 3 and 4, deletions, present in one patient. The genotype‐phenotype association correlates with the reported in the literature, with the exception of one patient.ConclusionThis molecular analysis allowed us to establish the causal variant of HB in 100% of patients, to provide the appropriate genetic counseling to each of the families, and to propose a more cost‐effective carrier analysis. Here, we reported the first variants in Colombian population with Hemophilia B, finding a new variant and one intron recurrent variant present in 35% of patients.

Mutation analysis and characterisation of F9 gene in haemophilia- B population of India

“…We recorded the stop-gain mutation p.R75W in 2 patients with severe HB, which have been described previously by Parrado Jara et al . (2020) [ 5 ], Radic et al . (2013) [ 16 ], Kwon et al .…”

“…It is also called “Christmas disorder”, after it was identified by Stephen Christmas in 1952 [ 3 ]. FIX activity can be classified as severely (<1%), moderately (1–5%), and mildly (5–30%) impaired [ 1 , 4 , 5 ]. HB is less common than hemophilia A (HA) (1 in 25,000 males vs. 1 in 5,000 males worldwide) [ 6 , 7 ].…”

Molecular analysis of 76 Chinese hemophilia B pedigrees and the identification of 10 novel mutations

“…Based on the reported spectrum of F9 mutations in different populations—for example, Americans, Colombians, Italians, Canadians, etc.—the spectrum of F9 mutations differs across populations (Belvini et al, 2005; Chen et al, 2020; Li et al, 2014; Natalia, Jayne, Shawn, Paula, & David, 2013; Parrado Jara, Yunis Hazbun, Linares, & Yunis Londoño, 2020). Therefore, enriching the FIX variant database enables us to analyze the distribution of F9 mutations in different populations and provides more detailed annotation information on these variants.…”

Cumplimiento de los indicadores de gestión del riesgo en salud del modelo de atención en pacientes con hemofilia A y B en una entidad administradora de planes de beneficios

“…La población provenía principalmente de los departamentos de Antioquia y Valle con cerca del 56.6% (Tabla 1).Del total de pacientes diagnosticados con hemofilia reportados en la CAC, 82.8% tenían hemofilia tipo A, con una condición severa (54.5%) y los diagnosticados con hemofilia tipo B (17.2%) fueron clasificados como severos el 38.1% (Tabla 2). información que difiere de la caracterización molecular de Parrado Jara, según el Informe Epidemiológico 2017 que mostraba un total de 362 hombres con HB en Colombia, de los cuales 38.1% tenían fenotipo severo, 36.4% fenotipo moderado y 23.4% fenotipo leve(14).…”