Familial chronic lymphocytic leukemia in Norway and Denmark. Comments on pleiotropy and birth order.
OBJECTIVE
To investigate the genetics of chronic lymphocytic leukemia (CLL).


METHODS
In 56 (7%) out of 800 CLL patients with concomitant malignant hematological disease, 51 families and 141 cases were ascertained.


RESULTS
106 cases (75%) of CLL, 27 cases (19%) of nonCLL and 8 cases (6%) of myeloproliferative disorders. Paternal disease was transmitted primarily to the youngest sons in the sibship while maternal disease was transmitted equally to all sibs, demonstrated by means of matrix conjugation and confirmed with Cox regression on parity and birth order (maternal-offspring combination: relative risk (RR), 95% confidence interval (CI)=1.47 (0.89 - 2.43), p=0.12, compared with paternal-offspring combination: RR=3.25, 95% CI=(1.57-6.72), p<0.001). The B-cell expression in familial and sporadic CLL was indistinguishable.


CONCLUSIONS
Parental genomic imprinting is pointed out as one possible mechanism behind this non-Mendelian genomic output.
Hematology Department, Oslo University Hospital Aker, Faculty Division, 235 Trondheimsvei, NO 0514 Oslo, Norway. viggo.jonsson@medisin.uio.no
Viggo
V
Jønsson
Geir E
GE
Tjønnfjord
Tom B
TB
Johannesen
Bernt
B
Ly
Jørgen H
JH
Olsen
Martin
M
Yuille
D001722:Birth Order; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005192:Family Health; D005220:Fathers; D005260:Female; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D006801:Humans; D040582:Inheritance Patterns; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D009035:Mothers; D009196:Myeloproliferative Disorders / Q000453:epidemiology / Q000235:genetics; D009664:Norway / Q000453:epidemiology; D010375:Pedigree; D011110:Polymorphism, Genetic; D012306:Risk