Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels

Franz Chavanne, Bernard C. Broughton, Daniela Pietra, Tiziana Nardo, Alison Browitt, Alan R. Lehmann, Miria Stefanini

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Xeroderma pigmentosum (XP)-C is one of the more common complementation groups of XP, but causative mutations have thus far been reported for only six cases (S. G. Khan et al., J. Investig. Dermatol., 115: 791-796, 1998; L. Li et al., Nat. Genet., 5: 413-417, 1993). We have now extended this analysis by investigating the genomic and coding sequence of the XPC gene, the level of expression of the XPC transcript and the status of the XPC protein in 12 unrelated patients, including all of the 8 Italian XP-C cases identified thus far and in 13 of their parents. Eighteen mutations were detected in the open reading frame of the XPC gene, 13 of which are relevant for the pathological phenotype. The mutations are distributed across the gene, with no indication of any hotspots or founder effects. Only 1 of the 13 relevant changes is a missense mutation, the remainder causing protein truncations as a result of nonsense mutations (3), frameshifts (6), deletion (1) or splicing abnormalities (2). These findings indicate that the XPC gene is not essential for cell proliferation and viability and that mutations causing minor structural alterations may not give an XP phenotype and may not, therefore, be identified clinically. XP13PV was the only patient carrying a missense mutation (Trp690Ser on the paternal allele). This was also the only patient in which the XPC transcript was present at a normal level and the XPC protein was detectable, although at a lower than normal level. No quantitative alterations in the transcript or protein levels were detected in the XP-C heterozygous parents. However, the expression of the normal allele predominated in all of them, except the father of XP13PV, which suggests the existence of a possible mechanism for monitoring the amount of the XPC protein.

Original languageEnglish
Pages (from-to)1974-1982
Number of pages9
JournalCancer Research
Volume60
Issue number7
Publication statusPublished - Apr 1 2000

Fingerprint

Xeroderma Pigmentosum
Mutation
Genes
Missense Mutation
Proteins
Parents
Alleles
Founder Effect
Viverridae
Phenotype
Nonsense Codon
Fathers
Open Reading Frames
Cell Survival
Cell Proliferation
Gene Expression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chavanne, F., Broughton, B. C., Pietra, D., Nardo, T., Browitt, A., Lehmann, A. R., & Stefanini, M. (2000). Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels. Cancer Research, 60(7), 1974-1982.

Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels. / Chavanne, Franz; Broughton, Bernard C.; Pietra, Daniela; Nardo, Tiziana; Browitt, Alison; Lehmann, Alan R.; Stefanini, Miria.

In: Cancer Research, Vol. 60, No. 7, 01.04.2000, p. 1974-1982.

Research output: Contribution to journalArticle

Chavanne, F, Broughton, BC, Pietra, D, Nardo, T, Browitt, A, Lehmann, AR & Stefanini, M 2000, 'Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels', Cancer Research, vol. 60, no. 7, pp. 1974-1982.
Chavanne, Franz ; Broughton, Bernard C. ; Pietra, Daniela ; Nardo, Tiziana ; Browitt, Alison ; Lehmann, Alan R. ; Stefanini, Miria. / Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels. In: Cancer Research. 2000 ; Vol. 60, No. 7. pp. 1974-1982.
@article{d6c1f9fe1ce844f39218dbc292d3bdbb,
title = "Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels",
abstract = "Xeroderma pigmentosum (XP)-C is one of the more common complementation groups of XP, but causative mutations have thus far been reported for only six cases (S. G. Khan et al., J. Investig. Dermatol., 115: 791-796, 1998; L. Li et al., Nat. Genet., 5: 413-417, 1993). We have now extended this analysis by investigating the genomic and coding sequence of the XPC gene, the level of expression of the XPC transcript and the status of the XPC protein in 12 unrelated patients, including all of the 8 Italian XP-C cases identified thus far and in 13 of their parents. Eighteen mutations were detected in the open reading frame of the XPC gene, 13 of which are relevant for the pathological phenotype. The mutations are distributed across the gene, with no indication of any hotspots or founder effects. Only 1 of the 13 relevant changes is a missense mutation, the remainder causing protein truncations as a result of nonsense mutations (3), frameshifts (6), deletion (1) or splicing abnormalities (2). These findings indicate that the XPC gene is not essential for cell proliferation and viability and that mutations causing minor structural alterations may not give an XP phenotype and may not, therefore, be identified clinically. XP13PV was the only patient carrying a missense mutation (Trp690Ser on the paternal allele). This was also the only patient in which the XPC transcript was present at a normal level and the XPC protein was detectable, although at a lower than normal level. No quantitative alterations in the transcript or protein levels were detected in the XP-C heterozygous parents. However, the expression of the normal allele predominated in all of them, except the father of XP13PV, which suggests the existence of a possible mechanism for monitoring the amount of the XPC protein.",
author = "Franz Chavanne and Broughton, {Bernard C.} and Daniela Pietra and Tiziana Nardo and Alison Browitt and Lehmann, {Alan R.} and Miria Stefanini",
year = "2000",
month = "4",
day = "1",
language = "English",
volume = "60",
pages = "1974--1982",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

TY - JOUR

T1 - Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels

AU - Chavanne, Franz

AU - Broughton, Bernard C.

AU - Pietra, Daniela

AU - Nardo, Tiziana

AU - Browitt, Alison

AU - Lehmann, Alan R.

AU - Stefanini, Miria

PY - 2000/4/1

Y1 - 2000/4/1

N2 - Xeroderma pigmentosum (XP)-C is one of the more common complementation groups of XP, but causative mutations have thus far been reported for only six cases (S. G. Khan et al., J. Investig. Dermatol., 115: 791-796, 1998; L. Li et al., Nat. Genet., 5: 413-417, 1993). We have now extended this analysis by investigating the genomic and coding sequence of the XPC gene, the level of expression of the XPC transcript and the status of the XPC protein in 12 unrelated patients, including all of the 8 Italian XP-C cases identified thus far and in 13 of their parents. Eighteen mutations were detected in the open reading frame of the XPC gene, 13 of which are relevant for the pathological phenotype. The mutations are distributed across the gene, with no indication of any hotspots or founder effects. Only 1 of the 13 relevant changes is a missense mutation, the remainder causing protein truncations as a result of nonsense mutations (3), frameshifts (6), deletion (1) or splicing abnormalities (2). These findings indicate that the XPC gene is not essential for cell proliferation and viability and that mutations causing minor structural alterations may not give an XP phenotype and may not, therefore, be identified clinically. XP13PV was the only patient carrying a missense mutation (Trp690Ser on the paternal allele). This was also the only patient in which the XPC transcript was present at a normal level and the XPC protein was detectable, although at a lower than normal level. No quantitative alterations in the transcript or protein levels were detected in the XP-C heterozygous parents. However, the expression of the normal allele predominated in all of them, except the father of XP13PV, which suggests the existence of a possible mechanism for monitoring the amount of the XPC protein.

AB - Xeroderma pigmentosum (XP)-C is one of the more common complementation groups of XP, but causative mutations have thus far been reported for only six cases (S. G. Khan et al., J. Investig. Dermatol., 115: 791-796, 1998; L. Li et al., Nat. Genet., 5: 413-417, 1993). We have now extended this analysis by investigating the genomic and coding sequence of the XPC gene, the level of expression of the XPC transcript and the status of the XPC protein in 12 unrelated patients, including all of the 8 Italian XP-C cases identified thus far and in 13 of their parents. Eighteen mutations were detected in the open reading frame of the XPC gene, 13 of which are relevant for the pathological phenotype. The mutations are distributed across the gene, with no indication of any hotspots or founder effects. Only 1 of the 13 relevant changes is a missense mutation, the remainder causing protein truncations as a result of nonsense mutations (3), frameshifts (6), deletion (1) or splicing abnormalities (2). These findings indicate that the XPC gene is not essential for cell proliferation and viability and that mutations causing minor structural alterations may not give an XP phenotype and may not, therefore, be identified clinically. XP13PV was the only patient carrying a missense mutation (Trp690Ser on the paternal allele). This was also the only patient in which the XPC transcript was present at a normal level and the XPC protein was detectable, although at a lower than normal level. No quantitative alterations in the transcript or protein levels were detected in the XP-C heterozygous parents. However, the expression of the normal allele predominated in all of them, except the father of XP13PV, which suggests the existence of a possible mechanism for monitoring the amount of the XPC protein.

UR - http://www.scopus.com/inward/record.url?scp=0034027382&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034027382&partnerID=8YFLogxK

M3 - Article

VL - 60

SP - 1974

EP - 1982

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 7

ER -