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PMID: 9042910 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature-termination codon.

American journal of human genetics ·Vol. 60 ·No. 3 ·1997-03-00 ·Pages 515-24

Edwards SJ, Gladwin AJ, Dixon MJ

Abstract

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified. In the current investigation, 25 previously undescribed mutations, which are spread throughout the gene, are presented. This brings the total reported to date to 35, which represents a detection rate of 60%. Of the mutations that have been reported to date, all but one result in the introduction of a premature-termination codon into the predicted protein, treacle. Moreover, the mutations are largely family specific, although a common 5 bp deletion in exon 24 (seven different families) and a recurrent splicing mutation in intron 3 (two different families) have been identified. This mutational spectrum supports the hypothesis that TCS results from haploinsufficiency.

MeSH Terms
Chromosomes, Human, Pair 5 Codon, Terminator/genetics Female Humans Male Mandibulofacial Dysostosis/genetics Mutation Nuclear Proteins/genetics Pedigree Phosphoproteins/genetics Polymorphism, Single-Stranded Conformational RNA Splicing
Chemicals
Codon, Terminator Nuclear Proteins Phosphoproteins TCOF1 protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Edwards S J
School of Biological Sciences and Department of Dental Medicine, University of Manchester, United Kingdom.
Gladwin A J
Dixon M J
References (44)
44 references, click to expand
  1. Mandibulo-facial dysostosis. (Treacher-Collins syndrome).
    Am J Dis Child. 1967 Apr;113(4):405-10 PMID: 6024864
  2. MANDIBULOFACIAL DYSOSTOSIS, A FAMILIAL STUDY OF FIVE GENERATIONS.
    J Pediatr. 1964 Aug;65:215-21 PMID: 14198411
  3. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  4. Penetrance and variability of major malformation syndromes associated with deafness.
    Birth Defects Orig Artic Ser. 1979;15(5B):207-26 PMID: 393321
  5. The ear deformities in mandibulofacial dysostosis (Treacher Collins syndrome).
    Clin Otolaryngol Allied Sci. 1981 Feb;6(1):15-28 PMID: 7273449
  6. Prenatal diagnosis of mandibulofacial dysostosis.
    Prenat Diagn. 1984 May-Jun;4(3):201-5 PMID: 6463027
  7. Hemifacial deficiency induced by a shift in dominance of the mouse mutation far: a possible genetic model for hemifacial microsomia.
    J Craniofac Genet Dev Biol. 1987;7(1):27-44 PMID: 3597720
  8. Mandibulofacial dysostosis (Treacher Collins syndrome): a new proposal for its pathogenesis.
    Am J Med Genet. 1987 Jun;27(2):359-72 PMID: 3474899
  9. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression.
    Nucleic Acids Res. 1987 Sep 11;15(17):7155-74 PMID: 3658675
  10. Detection and localization of single base changes by denaturing gradient gel electrophoresis.
    Methods Enzymol. 1987;155:501-27 PMID: 3431470
  11. Retinoic-acid-induced limb malformations resulting from apical ectodermal ridge cell death.
    Teratology. 1988 Jun;37(6):527-37 PMID: 3165225
  12. Attachment of a 40-base-pair G + C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes.
    Proc Natl Acad Sci U S A. 1989 Jan;86(1):232-6 PMID: 2643100
  13. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms.
    Proc Natl Acad Sci U S A. 1989 Apr;86(8):2766-70 PMID: 2565038
  14. Dysmorphogenesis of the mandible, zygoma, and middle ear ossicles in hemifacial microsomia and mandibulofacial dysostosis.
    Am J Med Genet. 1989 Jan;32(1):27-31 PMID: 2705480
  15. Pathogenesis of cleft palate in Treacher Collins, Nager, and Miller syndromes.
    Cleft Palate J. 1989 Jul;26(3):209-16; discussion 216 PMID: 2758673
  16. Nonsense mutations in the dihydrofolate reductase gene affect RNA processing.
    Mol Cell Biol. 1989 Jul;9(7):2868-80 PMID: 2779551
  17. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction.
    Genomics. 1989 Nov;5(4):874-9 PMID: 2687159
  18. Translation to near the distal end of the penultimate exon is required for normal levels of spliced triosephosphate isomerase mRNA.
    Mol Cell Biol. 1990 Oct;10(10):5215-25 PMID: 2398889
  19. Association of Treacher Collins syndrome and translocation 6p21.31/16p13.11: exclusion of the locus from these candidate regions.
    Am J Hum Genet. 1991 Feb;48(2):274-80 PMID: 1671319
  20. Prenatal ultrasonic diagnosis of mandibulofacial dysostosis (Treacher Collins syndrome).
    J Clin Ultrasound. 1991 Feb;19(2):124-7 PMID: 1847948
  21. The gene for Treacher Collins syndrome maps to the long arm of chromosome 5.
    Am J Hum Genet. 1991 Jul;49(1):17-22 PMID: 1676560
  22. Mapping the Treacher Collins syndrome locus to 5q31.3----q33.3.
    Genomics. 1991 Sep;11(1):193-8 PMID: 1765376
  23. Detecting single base substitutions as heteroduplex polymorphisms.
    Genomics. 1992 Feb;12(2):301-6 PMID: 1740339
  24. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism.
    Science. 1992 Oct 30;258(5083):806-8 PMID: 1439789
  25. The skipping of constitutive exons in vivo induced by nonsense mutations.
    Science. 1993 Jan 29;259(5095):680-3 PMID: 8430317
  26. Narrowing the position of the Treacher Collins syndrome locus to a small interval between three new microsatellite markers at 5q32-33.1.
    Am J Hum Genet. 1993 May;52(5):907-14 PMID: 8488840
  27. Genetic and physical mapping of the Treacher Collins syndrome locus: refinement of the localization to chromosome 5q32-33.2.
    Hum Mol Genet. 1992 Jul;1(4):249-53 PMID: 1303194
  28. The sensitivity of single-strand conformation polymorphism analysis for the detection of single base substitutions.
    Genomics. 1993 May;16(2):325-32 PMID: 8314571
  29. Four novel FBN1 mutations: significance for mutant transcript level and EGF-like domain calcium binding in the pathogenesis of Marfan syndrome.
    Genomics. 1993 Aug;17(2):468-75 PMID: 8406497
  30. A mutation in CFTR produces different phenotypes depending on chromosomal background.
    Nat Genet. 1993 Nov;5(3):274-8 PMID: 7506096
  31. Genetic and physical mapping of the Treacher Collins syndrome locus with respect to loci in the chromosome 5q3 region.
    Genomics. 1993 Oct;18(1):7-13 PMID: 8276417
  32. A combined genetic and radiation hybrid map surrounding the Treacher Collins syndrome locus on chromosome 5q.
    Hum Mol Genet. 1993 Nov;2(11):1785-92 PMID: 8281138
  33. A YAC contig encompassing the Treacher Collins syndrome critical region at 5q31.3-32.
    Am J Hum Genet. 1994 Aug;55(2):372-8 PMID: 8037214
  34. Recurrence of Treacher Collins' syndrome with sonographic findings.
    Mil Med. 1994 Mar;159(3):250-2 PMID: 8041477
  35. Treacher Collins syndrome: correlation between clinical and genetic linkage studies.
    Clin Dysmorphol. 1994 Apr;3(2):96-103 PMID: 8055143
  36. Craniofacial syndromes: no such thing as a single gene disease.
    Nat Genet. 1995 Feb;9(2):101-3 PMID: 7719329
  37. The Treacher Collins syndrome. A clinical, radiological, and genetic linkage study on two pedigrees.
    Arch Otolaryngol Head Neck Surg. 1995 May;121(5):509-14 PMID: 7727083
  38. Cloning of the human heparan sulfate-N-deacetylase/N-sulfotransferase gene from the Treacher Collins syndrome candidate region at 5q32-q33.1.
    Genomics. 1995 Mar 20;26(2):239-44 PMID: 7601448
  39. Prenatal sonographic diagnosis of Treacher Collins syndrome: a case and review of the literature.
    Am J Perinatol. 1995 Nov;12(6):416-9 PMID: 8579653
  40. Transcriptional map of the Treacher Collins candidate gene region.
    Genome Res. 1996 Jan;6(1):26-34 PMID: 8681136
  41. Prenatal diagnosis in Treacher Collins syndrome using combined linkage analysis and ultrasound imaging.
    J Med Genet. 1996 Jul;33(7):603-6 PMID: 8818950
  42. Treacher Collins syndrome.
    Hum Mol Genet. 1996;5 Spec No:1391-6 PMID: 8875242
  43. Treacher Collins syndrome may result from insertions, deletions or splicing mutations, which introduce a termination codon into the gene.
    Hum Mol Genet. 1996 Oct;5(10):1533-8 PMID: 8894686
  44. Older paternal age and fresh gene mutation: data on additional disorders.
    J Pediatr. 1975 Jan;86(1):84-8 PMID: 1110452
Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Published
1997-03-00
Pages
515-24
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1712503
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source PMC Full Text View journal details
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