• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of ajhgLink to Publisher's site
Am J Hum Genet. Jun 1999; 64(6): 1604–1616.
PMCID: PMC1377903

X-linked late-onset sensorineural deafness caused by a deletion involving OA1 and a novel gene containing WD-40 repeats.

Abstract

We have identified a novel gene, transducin (beta)-like 1 (TBL1), in the Xp22.3 genomic region, that shows high homology with members of the WD-40-repeat protein family. The gene contains 18 exons spanning approximately 150 kb of the genomic region adjacent to the ocular albinism gene (OA1) on the telomeric side. However, unlike OA1, TBL1 is transcribed from telomere to centromere. Northern analysis indicates that TBL1 is ubiquitously expressed, with two transcripts of approximately 2.1 kb and 6.0 kb. The open reading frame encodes a 526-amino acid protein, which shows the presence of six beta-transducin repeats (WD-40 motif) in the C-terminal domain. The homology with known beta-subunits of G proteins and other WD-40-repeat containing proteins is restricted to the WD-40 motif. Genomic analysis revealed that the gene is either partly or entirely deleted in patients carrying Xp22.3 terminal deletions. The complexity of the contiguous gene-syndrome phenotype shared by these patients depends on the number of known disease genes involved in the deletions. Interestingly, one patient carrying a microinterstitial deletion involving the 3' portion of both TBL1 and OA1 shows the OA1 phenotype associated with X-linked late-onset sensorineural deafness. We postulate an involvement of TBL1 in the pathogenesis of the ocular albinism with late-onset sensorineural deafness phenotype.

Full Text

The Full Text of this article is available as a PDF (746K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Agulnik AI, Mitchell MJ, Mattei MG, Borsani G, Avner PA, Lerner JL, Bishop CE. A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human. Hum Mol Genet. 1994 Jun;3(6):879–884. [PubMed]
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. [PMC free article] [PubMed]
  • Bassi MT, Bergen AA, Wapenaar MC, Schiaffino MV, van Schooneveld M, Yates JR, Charles SJ, Meitinger T, Ballabio A. A submicroscopic deletion in a patient with isolated X-linked ocular albinism (OA1). Hum Mol Genet. 1994 Apr;3(4):647–648. [PubMed]
  • Bassi MT, Schiaffino MV, Renieri A, De Nigris F, Galli L, Bruttini M, Gebbia M, Bergen AA, Lewis RA, Ballabio A. Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome. Nat Genet. 1995 May;10(1):13–19. [PubMed]
  • Brown CJ, Flenniken AM, Williams BR, Willard HF. X chromosome inactivation of the human TIMP gene. Nucleic Acids Res. 1990 Jul 25;18(14):4191–4195. [PMC free article] [PubMed]
  • Davis AC. The prevalence of hearing impairment and reported hearing disability among adults in Great Britain. Int J Epidemiol. 1989 Dec;18(4):911–917. [PubMed]
  • del Castillo I, Villamar M, Sarduy M, Romero L, Herraiz C, Hernández FJ, Rodríguez M, Borrás I, Montero A, Bellón J, et al. A novel locus for non-syndromic sensorineural deafness (DFN6) maps to chromosome Xp22. Hum Mol Genet. 1996 Sep;5(9):1383–1387. [PubMed]
  • Disteche CM, Dinulos MB, Bassi MT, Elliott RW, Rugarli EI. Mapping of the murine tbl1 gene reveals a new rearrangement between mouse and human X Chromosomes. Mamm Genome. 1998 Dec;9(12):1062–1064. [PubMed]
  • Ferrero GB, Franco B, Roth EJ, Firulli BA, Borsani G, Delmas-Mata J, Weissenbach J, Halley G, Schlessinger D, Chinault AC, et al. An integrated physical and genetic map of a 35 Mb region on chromosome Xp22.3-Xp21.3. Hum Mol Genet. 1995 Oct;4(10):1821–1827. [PubMed]
  • Fong HK, Hurley JB, Hopkins RS, Miake-Lye R, Johnson MS, Doolittle RF, Simon MI. Repetitive segmental structure of the transducin beta subunit: homology with the CDC4 gene and identification of related mRNAs. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2162–2166. [PMC free article] [PubMed]
  • Franco B, Guioli S, Pragliola A, Incerti B, Bardoni B, Tonlorenzi R, Carrozzo R, Maestrini E, Pieretti M, Taillon-Miller P, et al. A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature. 1991 Oct 10;353(6344):529–536. [PubMed]
  • Franco B, Meroni G, Parenti G, Levilliers J, Bernard L, Gebbia M, Cox L, Maroteaux P, Sheffield L, Rappold GA, et al. A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy. Cell. 1995 Apr 7;81(1):15–25. [PubMed]
  • Lalwani AK, Brister JR, Fex J, Grundfast KM, Pikus AT, Ploplis B, San Agustin T, Skarka H, Wilcox ER. A new nonsyndromic X-linked sensorineural hearing impairment linked to Xp21.2. Am J Hum Genet. 1994 Oct;55(4):685–694. [PMC free article] [PubMed]
  • Lovett M. Fishing for complements: finding genes by direct selection. Trends Genet. 1994 Oct;10(10):352–357. [PubMed]
  • Mannhaupt G, Stucka R, Ehnle S, Vetter I, Feldmann H. Analysis of a 70 kb region on the right arm of yeast chromosome II. Yeast. 1994 Oct;10(10):1363–1381. [PubMed]
  • Marck C. 'DNA Strider': a 'C' program for the fast analysis of DNA and protein sequences on the Apple Macintosh family of computers. Nucleic Acids Res. 1988 Mar 11;16(5):1829–1836. [PMC free article] [PubMed]
  • Neer EJ, Schmidt CJ, Nambudripad R, Smith TF. The ancient regulatory-protein family of WD-repeat proteins. Nature. 1994 Sep 22;371(6495):297–300. [PubMed]
  • O'Donnell FE, Jr, Hambrick GW, Jr, Green WR, Iliff WJ, Stone DL. X-linked ocular albinism. An oculocutaneous macromelanosomal disorder. Arch Ophthalmol. 1976 Nov;94(11):1883–1892. [PubMed]
  • Quaderi NA, Schweiger S, Gaudenz K, Franco B, Rugarli EI, Berger W, Feldman GJ, Volta M, Andolfi G, Gilgenkrantz S, et al. Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22. Nat Genet. 1997 Nov;17(3):285–291. [PubMed]
  • Rubin GM. Around the genomes: the Drosophila genome project. Genome Res. 1996 Feb;6(2):71–79. [PubMed]
  • Rugarli EI, Lutz B, Kuratani SC, Wawersik S, Borsani G, Ballabio A, Eichele G. Expression pattern of the Kallmann syndrome gene in the olfactory system suggests a role in neuronal targeting. Nat Genet. 1993 May;4(1):19–26. [PubMed]
  • Schaefer L, Ferrero GB, Grillo A, Bassi MT, Roth EJ, Wapenaar MC, van Ommen GJ, Mohandas TK, Rocchi M, Zoghbi HY, et al. A high resolution deletion map of human chromosome Xp22. Nat Genet. 1993 Jul;4(3):272–279. [PubMed]
  • Schiaffino MV, Bassi MT, Rugarli EI, Renieri A, Galli L, Ballabio A. Cloning of a human homologue of the Xenopus laevis APX gene from the ocular albinism type 1 critical region. Hum Mol Genet. 1995 Mar;4(3):373–382. [PubMed]
  • Schnur RE, Gao M, Wick PA, Keller M, Benke PJ, Edwards MJ, Grix AW, Hockey A, Jung JH, Kidd KK, et al. OA1 mutations and deletions in X-linked ocular albinism. Am J Hum Genet. 1998 Apr;62(4):800–809. [PMC free article] [PubMed]
  • Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB. Crystal structure of a G-protein beta gamma dimer at 2.1A resolution. Nature. 1996 Jan 25;379(6563):369–374. [PubMed]
  • Sonnhammer EL, Eddy SR, Durbin R. Pfam: a comprehensive database of protein domain families based on seed alignments. Proteins. 1997 Jul;28(3):405–420. [PubMed]
  • Spevak W, Keiper BD, Stratowa C, Castañn MJ. Saccharomyces cerevisiae cdc15 mutants arrested at a late stage in anaphase are rescued by Xenopus cDNAs encoding N-ras or a protein with beta-transducin repeats. Mol Cell Biol. 1993 Aug;13(8):4953–4966. [PMC free article] [PubMed]
  • Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. [PMC free article] [PubMed]
  • van Slegtenhorst MA, Bassi MT, Borsani G, Wapenaar MC, Ferrero GB, de Conciliis L, Rugarli EI, Grillo A, Franco B, Zoghbi HY, et al. A gene from the Xp22.3 region shares homology with voltage-gated chloride channels. Hum Mol Genet. 1994 Apr;3(4):547–552. [PubMed]
  • Wapenaar MC, Bassi MT, Schaefer L, Grillo A, Ferrero GB, Chinault AC, Ballabio A, Zoghbi HY. The genes for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects (MLS): cloning and characterization of the critical regions. Hum Mol Genet. 1993 Jul;2(7):947–952. [PubMed]
  • Winship I, Gericke G, Beighton P. X-linked inheritance of ocular albinism with late-onset sensorineural deafness. Am J Med Genet. 1984 Dec;19(4):797–803. [PubMed]
  • Winship IM, Babaya M, Ramesar RS. X-linked ocular albinism and sensorineural deafness: linkage to Xp22.3. Genomics. 1993 Nov;18(2):444–445. [PubMed]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Gene
    Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene
    HomoloGene links
  • MedGen
    MedGen
    Related information in MedGen
  • Nucleotide
    Nucleotide
    Published Nucleotide sequences
  • OMIM
    OMIM
    OMIM record citing PubMed
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...