Origin of pathogenic variant and mosaicism in families with a sporadic case of haemophilia B.
Haemophilia
; 30(3): 774-779, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38632836
ABSTRACT
INTRODUCTION:
Of newly diagnosed cases of haemophilia B, the proportion of sporadic cases is usually 50% of severe cases and 25% of moderate/mild cases. However, cases presumed to be sporadic due to family history may not always be sporadic. Few case reports have been published on mosaicism in haemophilia B.AIM:
The present study aimed to trace the origin of the pathogenic variant in a well-defined cohort of sporadic cases of haemophilia B by haplotyping markers. It also aimed to determine the frequency of mosaicism in presumed non-carrier mothers.METHODS:
The study group was 40 families, each with a sporadic case of haemophilia B analysed in two-to-three generations by Sanger sequencing, haplotyping and using the sensitive droplet digital polymerase chain reaction (ddPCR) technique.RESULTS:
In 31/40 (78%) of the families, the mother carried the same pathogenic variant as her son, while Sanger sequencing showed that 9/40 (22%) of the mothers did not carry this variant. Of these variants, 2/9 (22%) were shown to be mosaics by using the ddPCR technique. 16/21 carrier mothers, with samples from three generations available, had a de novo pathogenic variant of which 14 derived from the healthy maternal grandfather.CONCLUSION:
The origin of the pathogenic variant in sporadic cases of haemophilia B is most often found in the X-chromosome derived from the maternal grandfather or, less often, from the maternal grandmother. Mosaic females seem to be found at the same frequency as in haemophilia A but at a lower percentage of the pathogenic variant.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hemophilia B
/
Mosaicism
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Haemophilia
Journal subject:
HEMATOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: