The genetic analysis of eight families with hemophilia B in Mongolia: Identification of two novel mutation

TL;DR

This study identified two new genetic mutations causing severe hemophilia B in Mongolian families and found few symptoms in female carriers.

Contribution

The study reports two novel mutations in the F9 gene associated with severe hemophilia B in Mongolia.

Findings

Two novel F9 gene variants (c.187_188del and c.1314_1314delA) were identified in patients with severe hemophilia B.

Only one of five genetically confirmed female carriers showed noticeable symptoms.

Variants were found in six out of eight families, but two mild cases had no detectable F9 mutations.

Abstract

This study aimed to conduct molecular diagnostics among individuals with hemophilia B (HB) and carriers of hemophilia in Mongolia.

Eight patients (six severe, two mild) with HB and their 12 female relatives were enrolled from eight families. Sanger sequence was performed for mutation identification. The questionnaire survey was conducted to evaluate carrier symptoms in female relatives.

Two families had a history of HB. A total of five different variants (c.223C > T; c.344A > G; c.464G > C; c.187_188del; and c.1314_1314delA) were identified in six patients with severe HB. Of these, two (c.187_188del and c.1314_1314delA) were novel. No variant in the entire F9 was found in two patients with mild HB. Nonsense c.223C > T (p.Arg75*) mutation was detected in two unrelated patients. Carrier testing identified five mothers as carriers, while one younger sister was a non‐carrier. The carrier status of six female relatives of the two mild patients remained undetermined. By questionnaire survey, only one of the five genetically identified carriers displayed noticeable symptoms of being a carrier.

The novel variants c.187_188del and c.1314_1314delA can cause severe hemophilia B. This study did not observe a significant association between symptoms and carrier status in the five carriers.

Variants in F9 gene were found in six out of eight families. Two variants were novel or not registered previously. Only one female relative displayed indicative symptoms of hemophilia carrier.

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