PAX genes and human neural tube defects

An amino acid substitution in PAX1 in a patient with spina bifida

F. A. Hol, M. P A Geurds, S. Chatkupt, Y. Y. Shugart, R. Balling, C. T R M Schrander-Stumpel, W. G. Johnson, B. C J Hamel, E. C M Mariman

Research output: Contribution to journalArticle

Abstract

From studies in the mouse and from the clinical and molecular analysis of patients with type 1 Waardenburg syndrome, particular members of the PAX gene family are suspected factors in the aetiology of human neural tube defects (NTD). To investigate the role of PAX1, PAX3, PAX7, and PAX9, allelic association studies were performed in 79 sporadic and 38 familial NTD patients from the Dutch population. Sequence variation was studied by SSC analysis of the paired domain regions of the PAX1, PAX7, and PAX9 genes and of the complete PAX3 gene. In one patient with spina bifida, a mutation in the PAX1 gene was detected changing the conserved amino acid Gln to His at position 42 in the paired domain of the protein. The mutation was inherited through the maternal line from the unaffected grandmother and was not detected in 300 controls. In the PAX3 gene, variation was detected at several sites including a Thr/Lys amino acid substitution in exon 6. All alleles were present among patients and controls in about the same frequencies. However, an increased frequency of the rare allele of a silent polymorphism in exon 2 was found in NTD patients, but no significant association was observed (p = 0.06). No sequence variation was observed in the paired domain of the PAX7 and PAX9 genes. Our findings so far do not support a major role of the PAX genes examined in the aetiology of NTD. However, the detection of a mutation in PAX1 suggests that, in principle, this gene can act as a risk factor for human NTD.

Original languageEnglish (US)
Pages (from-to)655-660
Number of pages6
JournalJournal of Medical Genetics
Volume33
Issue number8
StatePublished - 1996
Externally publishedYes

Fingerprint

Spinal Dysraphism
Neural Tube Defects
Amino Acid Substitution
Genes
Mutation
Exons
Waardenburg Syndrome
Gene Frequency
Alleles
Mothers
Amino Acids

Keywords

  • Neural tube defects
  • PAX genes
  • Spina bifida

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Hol, F. A., Geurds, M. P. A., Chatkupt, S., Shugart, Y. Y., Balling, R., Schrander-Stumpel, C. T. R. M., ... Mariman, E. C. M. (1996). PAX genes and human neural tube defects: An amino acid substitution in PAX1 in a patient with spina bifida. Journal of Medical Genetics, 33(8), 655-660.

PAX genes and human neural tube defects : An amino acid substitution in PAX1 in a patient with spina bifida. / Hol, F. A.; Geurds, M. P A; Chatkupt, S.; Shugart, Y. Y.; Balling, R.; Schrander-Stumpel, C. T R M; Johnson, W. G.; Hamel, B. C J; Mariman, E. C M.

In: Journal of Medical Genetics, Vol. 33, No. 8, 1996, p. 655-660.

Research output: Contribution to journalArticle

Hol, FA, Geurds, MPA, Chatkupt, S, Shugart, YY, Balling, R, Schrander-Stumpel, CTRM, Johnson, WG, Hamel, BCJ & Mariman, ECM 1996, 'PAX genes and human neural tube defects: An amino acid substitution in PAX1 in a patient with spina bifida', Journal of Medical Genetics, vol. 33, no. 8, pp. 655-660.
Hol FA, Geurds MPA, Chatkupt S, Shugart YY, Balling R, Schrander-Stumpel CTRM et al. PAX genes and human neural tube defects: An amino acid substitution in PAX1 in a patient with spina bifida. Journal of Medical Genetics. 1996;33(8):655-660.
Hol, F. A. ; Geurds, M. P A ; Chatkupt, S. ; Shugart, Y. Y. ; Balling, R. ; Schrander-Stumpel, C. T R M ; Johnson, W. G. ; Hamel, B. C J ; Mariman, E. C M. / PAX genes and human neural tube defects : An amino acid substitution in PAX1 in a patient with spina bifida. In: Journal of Medical Genetics. 1996 ; Vol. 33, No. 8. pp. 655-660.
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