PMID- 10094191
OWN - NLM
STAT- MEDLINE
DCOM- 19990513
LR  - 20220129
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 7
IP  - 1
DP  - 1999 Jan
TI  - Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene.
PG  - 52-9
AB  - Fanconi anaemia (FA) is a genetically heterogeneous autosomal recessive disorder 
      associated with chromosomal fragility, bone-marrow failure, congenital
      abnormalities and cancer. The gene for complementation group A (FAA), which
      accounts for 60-65% of all cases, has been cloned, and is composed of an open
      reading frame of 4.3 kb, which is distributed among 43 exons. We have
      investigated the molecular pathology of FA by screening the FAA gene for
      mutations in a panel of 90 patients identified by the European FA research group,
      EUFAR. A highly heterogeneous spectrum of mutations was identified, with 31
      different mutations being detected in 34 patients. The mutations were scattered
      throughout the gene, and most are likely to result in the absence of the FAA
      protein. A surprisingly high frequency of intragenic deletions was detected,
      which removed between 1 and 30 exons from the gene. Most microdeletions and
      insertions occurred at homopolymeric tracts or direct repeats within the coding
      sequence. These features have not been observed in the other FA gene which has
      been cloned to date (FAC) and may be indicative of a higher mutation rate in FAA.
      This would explain why FA group A is much more common than the other
      complementation groups. The heterogeneity of the mutation spectrum and the
      frequency of intragenic deletions present a considerable challenge for the
      molecular diagnosis of FA. A scan of the entire coding sequence of the FAA gene
      may be required to detect the causative mutations, and scanning protocols will
      have to include methods which will detect the deletions in compound
      heterozygotes.
FAU - Wijker, M
AU  - Wijker M
AD  - Department of Human Genetics, Free University of Amsterdam, The Netherlands.
FAU - Morgan, N V
AU  - Morgan NV
FAU - Herterich, S
AU  - Herterich S
FAU - van Berkel, C G
AU  - van Berkel CG
FAU - Tipping, A J
AU  - Tipping AJ
FAU - Gross, H J
AU  - Gross HJ
FAU - Gille, J J
AU  - Gille JJ
FAU - Pals, G
AU  - Pals G
FAU - Savino, M
AU  - Savino M
FAU - Altay, C
AU  - Altay C
FAU - Mohan, S
AU  - Mohan S
FAU - Dokal, I
AU  - Dokal I
FAU - Cavenagh, J
AU  - Cavenagh J
FAU - Marsh, J
AU  - Marsh J
FAU - van Weel, M
AU  - van Weel M
FAU - Ortega, J J
AU  - Ortega JJ
FAU - Schuler, D
AU  - Schuler D
FAU - Samochatova, E
AU  - Samochatova E
FAU - Karwacki, M
AU  - Karwacki M
FAU - Bekassy, A N
AU  - Bekassy AN
FAU - Abecasis, M
AU  - Abecasis M
FAU - Ebell, W
AU  - Ebell W
FAU - Kwee, M L
AU  - Kwee ML
FAU - de Ravel, T
AU  - de Ravel T
FAU - CG Mathew
AU  - CG Mathew
AU  - et al.
LA  - eng
GR  - E.0688/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (DNA Primers)
SB  - IM
MH  - Base Sequence
MH  - DNA Primers
MH  - Exons
MH  - Fanconi Anemia/ethnology/*genetics
MH  - Genetic Complementation Test
MH  - Heterozygote
MH  - Humans
MH  - *Mutation
EDAT- 1999/03/27 00:00
MHDA- 1999/03/27 00:01
CRDT- 1999/03/27 00:00
PHST- 1999/03/27 00:00 [pubmed]
PHST- 1999/03/27 00:01 [medline]
PHST- 1999/03/27 00:00 [entrez]
AID - 10.1038/sj.ejhg.5200248 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 1999 Jan;7(1):52-9. doi: 10.1038/sj.ejhg.5200248.