Somatic Origin of Inherited Haemophilia A

Overview

Journal Hum Genet

Specialty Genetics

Date 1990 Aug 1

PMID 1975557

Citations 25

Authors

A H Brocker-Vriends

E Briet

J C Dreesen

B Bakker

P Reitsma

H Pannekoek

J J van de Kamp

P L Pearson

Affiliations

Soon will be listed here.

Abstract

We found a partial deletion of the clotting factor VIII gene of about 2000 bp, spanning exon 5 and part of intervening sequence 4 and 5 in an isolated patient with severe haemophilia A. The mother of the patient, who appeared to be a non-carrier on the basis of coagulation assays and restriction fragment length polymorphism analysis in the family, turned out to be a mosaic for the deletion, not only in her germ cells, but also in various somatic cells. These findings suggest that the mutation is the result of an event in early embryogenesis. If mosaicism for a mutation, either gonadal or somatic, proves to be a common phenomenon in human genetics, it is imperative to reconsider genetic risks for (future) sibs of any apparently new mutant of a hereditary disease.

Citing Articles

Detection of mosaics in hemophilia A by deep Ion Torrent sequencing and droplet digital PCR.

Manderstedt E, Nilsson R, Ljung R, Lind-Hallden C, Astermark J, Hallden C Res Pract Thromb Haemost. 2020; 4(7):1121-1130.

PMID: 33134778 PMC: 7590296. DOI: 10.1002/rth2.12425.

Genetic analysis of haemophilia A in Bulgaria.

Petkova R, Chakarov S, Kremensky I BMC Blood Disord. 2004; 4:2.

PMID: 15035673 PMC: 387827. DOI: 10.1186/1471-2326-4-2.

A case of PDH-E1 alpha mosaicism in a male patient with severe metabolic lactic acidosis.

Seyda A, Chun K, Packman S, Robinson B J Inherit Metab Dis. 2002; 24(5):551-9.

PMID: 11757583 DOI: 10.1023/a:1012463726810.

Somatic mosaicism in hemophilia A: a fairly common event.

Leuer M, Oldenburg J, Lavergne J, Ludwig M, Fregin A, Eigel A Am J Hum Genet. 2001; 69(1):75-87.

PMID: 11410838 PMC: 1226050. DOI: 10.1086/321285.

Germline and somatic mosaicism in a female carrier of Hunter disease.

Froissart R, Maire I, Bonnet V, Levade T, Bozon D J Med Genet. 1997; 34(2):137-40.

PMID: 9039991 PMC: 1050868. DOI: 10.1136/jmg.34.2.137.

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