TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - van Kuilenburg, André B. P.
A1  - Meijer, Judith
A1  - Mul, Adri N. P. M.
A1  - Hennekam, Raoul C. M.
A1  - Hoovers, Jan M. N.
A1  - Die-Smulders, Christine E. M. de
A1  - Weber, Peter
A1  - Mori, Andrea Capone
A1  - Bierau, Jörgen
A1  - Fowler, Brian
A1  - Macke, Klaus
A1  - Sass, Jörn Oliver
A1  - Meinsma, Rutger
A1  - Hennermann, Julia B.
A1  - Miny, Peter
A1  - Zoetekouw, Lida
A1  - Vijzelaar, Raymon
A1  - Nicolai, Joost
A1  - Ylstra, Bauke
A1  - Rubio-Gozalbo, M. Estela
T1  - Analysis of severely affected patients with dihydropyrimidine dehydrogenase deficiency reveals large intragenic rearrangements of DPYD and a de novo interstitial deletion del(1)(p13.3p21.3)
JF  - Human Genetics
N2  - Dihydropyrimidine dehydrogenase (DPD) deficiency is an infrequently described autosomal recessive disorder of the pyrimidine degradation pathway and can lead to mental and motor retardation and convulsions. DPD deficiency is also known to cause a potentially lethal toxicity following administration of the antineoplastic agent 5-fluorouracil. In an ongoing study of 72 DPD deficient patients, we analysed the molecular background of 5 patients in more detail in whom initial sequence analysis did not reveal pathogenic mutations. In three patients, a 13.8 kb deletion of exon 12 was found and in one patient a 122 kb deletion of exon 14–16 of DPYD. In the fifth patient, a c.299_302delTCAT mutation in exon 4 was found and also loss of heterozygosity of the entire DPD gene. Further analysis demonstrated a de novo deletion of approximately 14 Mb of chromosome 1p13.3–1p21.3, which includes DPYD. Haploinsufficiency of NTNG1, LPPR4, GPSM2, COL11A1 and VAV3 might have contributed to the severe psychomotor retardation and unusual craniofacial features in this patient. Our study showed for the first time the presence of genomic deletions affecting DPYD in 7% (5/72) of all DPD deficient patients. Therefore, screening of DPD deficient patients for genomic deletions should be considered.
SN  - 0340-6717
SS  - 0340-6717
U6  - https://doi.org/10.1007/s00439-009-0653-6
DO  - https://doi.org/10.1007/s00439-009-0653-6
PM  - 19296131
VL  - 125
IS  - 5-6
SP  - 581
EP  - 590
PB  - Springer
ER  -