Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene

M. Wijker, N. V. Morgan, S. Herterich, C. G M Van Berkel, A. J. Tipping, H. J. Gross, J. J P Gille, G. Pals, M. Savino, C. Altay, S. Mohan, I. Dokal, J. Cavenagh, J. Marsh, M. Van Weel, J. J. Ortega, D. Schuler, E. Samochatova, M. Karwacki, A. N. Bekassy & 12 others M. Abecasis, W. Ebell, M. L. Kwee, T. De Ravel, R. A. Gibson, E. Gluckman, F. Arwert, H. Joenje, A. Savoia, H. Hoehn, J. C. Pronk, C. G. Mathew

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)52-59
Number of pages8
JournalEuropean Journal of Human Genetics
Volume7
Issue number1
Publication statusPublished - Jan 1999

Fingerprint

Fanconi Anemia
Mutation
Genes
Mutation Rate
Exons
Chromosome Fragility
Molecular Pathology
Nucleic Acid Repetitive Sequences
Heterozygote
Open Reading Frames
Bone Marrow
Research
Neoplasms
Proteins

Keywords

  • FAA gene
  • Fanconi anaemia
  • Mutations

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Wijker, M., Morgan, N. V., Herterich, S., Van Berkel, C. G. M., Tipping, A. J., Gross, H. J., ... Mathew, C. G. (1999). Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene. European Journal of Human Genetics, 7(1), 52-59.

Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene. / Wijker, M.; Morgan, N. V.; Herterich, S.; Van Berkel, C. G M; Tipping, A. J.; Gross, H. J.; Gille, J. J P; Pals, G.; Savino, M.; Altay, C.; Mohan, S.; Dokal, I.; Cavenagh, J.; Marsh, J.; Van Weel, M.; Ortega, J. J.; Schuler, D.; Samochatova, E.; Karwacki, M.; Bekassy, A. N.; Abecasis, M.; Ebell, W.; Kwee, M. L.; De Ravel, T.; Gibson, R. A.; Gluckman, E.; Arwert, F.; Joenje, H.; Savoia, A.; Hoehn, H.; Pronk, J. C.; Mathew, C. G.

In: European Journal of Human Genetics, Vol. 7, No. 1, 01.1999, p. 52-59.

Research output: Contribution to journalArticle

Wijker, M, Morgan, NV, Herterich, S, Van Berkel, CGM, Tipping, AJ, Gross, HJ, Gille, JJP, Pals, G, Savino, M, Altay, C, Mohan, S, Dokal, I, Cavenagh, J, Marsh, J, Van Weel, M, Ortega, JJ, Schuler, D, Samochatova, E, Karwacki, M, Bekassy, AN, Abecasis, M, Ebell, W, Kwee, ML, De Ravel, T, Gibson, RA, Gluckman, E, Arwert, F, Joenje, H, Savoia, A, Hoehn, H, Pronk, JC & Mathew, CG 1999, 'Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene', European Journal of Human Genetics, vol. 7, no. 1, pp. 52-59.
Wijker M, Morgan NV, Herterich S, Van Berkel CGM, Tipping AJ, Gross HJ et al. Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene. European Journal of Human Genetics. 1999 Jan;7(1):52-59.
Wijker, M. ; Morgan, N. V. ; Herterich, S. ; Van Berkel, C. G M ; Tipping, A. J. ; Gross, H. J. ; Gille, J. J P ; Pals, G. ; Savino, M. ; Altay, C. ; Mohan, S. ; Dokal, I. ; Cavenagh, J. ; Marsh, J. ; Van Weel, M. ; Ortega, J. J. ; Schuler, D. ; Samochatova, E. ; Karwacki, M. ; Bekassy, A. N. ; Abecasis, M. ; Ebell, W. ; Kwee, M. L. ; De Ravel, T. ; Gibson, R. A. ; Gluckman, E. ; Arwert, F. ; Joenje, H. ; Savoia, A. ; Hoehn, H. ; Pronk, J. C. ; Mathew, C. G. / Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene. In: European Journal of Human Genetics. 1999 ; Vol. 7, No. 1. pp. 52-59.
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AU - Tipping, A. J.

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AU - Gille, J. J P

AU - Pals, G.

AU - Savino, M.

AU - Altay, C.

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AU - Abecasis, M.

AU - Ebell, W.

AU - Kwee, M. L.

AU - De Ravel, T.

AU - Gibson, R. A.

AU - Gluckman, E.

AU - Arwert, F.

AU - Joenje, H.

AU - Savoia, A.

AU - Hoehn, H.

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AU - Mathew, C. G.

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