• 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 1993; 52(6): 1046–1052.
PMCID: PMC1682275

Linkage mapping of a severe X-linked mental retardation syndrome.

Abstract

A four-generation Swedish family with a new type of X-linked mental retardation syndrome was recently reported by Gustavson et al. The complex syndrome includes microcephaly, severe mental retardation, optical atrophy with decreased vision or blindness, severe hearing defect, characteristic facial features, spasticity, seizures, and restricted joint motility. The patients die during infancy or early in childhood. Twenty-one family members, including two affected males, were available for study. Linkage analysis was conducted in the family by using 11 RFLP markers and 10 VNTR markers spread along the X chromosome. A hypervariable short tandem repeat of DXS294 at Xq26 showed a peak two-point lod score of 3.35 at zero recombination fraction. Calculations using the same markers revealed a multipoint peak lod score of 3.65 at DXS294. Crossover events with the centromeric marker DXS424 and the telomeric marker DXS297 delimit a probable region for the gene localization. It is noteworthy that hte disease loci of two other syndromes with overlapping clinical manifestations recently were shown by Turner et al. and Pettigrew et al. to be linked to markers at Xq26.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1021K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aldridge J, Kunkel L, Bruns G, Tantravahi U, Lalande M, Brewster T, Moreau E, Wilson M, Bromley W, Roderick T, et al. A strategy to reveal high-frequency RFLPs along the human X chromosome. Am J Hum Genet. 1984 May;36(3):546–564. [PMC free article] [PubMed]
  • Arena JF, Lubs HA. Computerized approach to X-linked mental retardation syndromes. Am J Med Genet. 1991 Feb-Mar;38(2-3):190–199. [PubMed]
  • Bakker E, Hofker MH, Goor N, Mandel JL, Wrogemann K, Davies KE, Kunkel LM, Willard HF, Fenton WA, Sandkuyl L, et al. Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy with closely linked RFLPs. Lancet. 1985 Mar 23;1(8430):655–658. [PubMed]
  • Boggs BA, Nussbaum RL. Two anonymous X-specific human sequences detecting restriction fragment length polymorphisms in region Xq26----qter. Somat Cell Mol Genet. 1984 Nov;10(6):607–613. [PubMed]
  • Camerino G, Grzeschik KH, Jaye M, De La Salle H, Tolstoshev P, Lecocq JP, Heilig R, Mandel JL. Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus). Proc Natl Acad Sci U S A. 1984 Jan;81(2):498–502. [PMC free article] [PubMed]
  • Gedeon AK, Richards RI, Mulley JC. Dinucleotide repeat polymorphisms at the DXS294 and DXS300 loci in Xq26. Nucleic Acids Res. 1991 Sep 25;19(18):5087–5087. [PMC free article] [PubMed]
  • Glass IA. X linked mental retardation. J Med Genet. 1991 Jun;28(6):361–371. [PMC free article] [PubMed]
  • Gustavson KH, Annerén G, Malmgren H, Dahl N, Ljunggren CG, Bäckman H. New X-linked syndrome with severe mental retardation, severely impaired vision, severe hearing defect, epileptic seizures, spasticity, restricted joint mobility, and early death. Am J Med Genet. 1993 Mar 1;45(5):654–658. [PubMed]
  • Hearne CM, Todd JA. Tetranucleotide repeat polymorphism at the HPRT locus. Nucleic Acids Res. 1991 Oct 11;19(19):5450–5450. [PMC free article] [PubMed]
  • Huang TH, Cottingham RW, Jr, Ledbetter DH, Zoghbi HY. Genetic mapping of four dinucleotide repeat loci, DXS453, DXS458, DXS454, and DXS424, on the X chromosome using multiplex polymerase chain reaction. Genomics. 1992 Jun;13(2):375–380. [PubMed]
  • Huang TH, Hejtmancik JF, Edwards A, Pettigrew AL, Herrera CA, Hammond HA, Caskey CT, Zoghbi HY, Ledbetter DH. Linkage of the gene for an X-linked mental retardation disorder to a hypervariable (AGAT)n repeat motif within the human hypoxanthine phosphoribosyltransferase (HPRT) locus (Xq26). Am J Hum Genet. 1991 Dec;49(6):1312–1319. [PMC free article] [PubMed]
  • Keats BJ, Sherman SL, Morton NE, Robson EB, Buetow KH, Cartwright PE, Chakravarti A, Francke U, Green PP, Ott J. Guidelines for human linkage maps. An International System for Human Linkage Maps (ISLM, 1990). Ann Hum Genet. 1991 Jan;55(Pt 1):1–6. [PubMed]
  • Kunkel LM, Smith KD, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Breg WR, Jones HW, Jr, Rary JM. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. [PMC free article] [PubMed]
  • Lathrop GM, Lalouel JM. Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet. 1984 Mar;36(2):460–465. [PMC free article] [PubMed]
  • Little RD, Pilia G, Johnson S, D'Urso M, Schlessinger D. Yeast artificial chromosomes spanning 8 megabases and 10-15 centimorgans of human cytogenetic band Xq26. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):177–181. [PMC free article] [PubMed]
  • Luty JA, Guo Z, Willard HF, Ledbetter DH, Ledbetter S, Litt M. Five polymorphic microsatellite VNTRs on the human X chromosome. Am J Hum Genet. 1990 Apr;46(4):776–783. [PMC free article] [PubMed]
  • Neri G, Chiurazzi P, Arena F, Lubs HA, Glass IA. XLMR genes: update 1992. Am J Med Genet. 43(1-2):373–382. [PubMed]
  • Oberlé I, Drayna D, Camerino G, White R, Mandel JL. The telomeric region of the human X chromosome long arm: presence of a highly polymorphic DNA marker and analysis of recombination frequency. Proc Natl Acad Sci U S A. 1985 May;82(9):2824–2828. [PMC free article] [PubMed]
  • Page DC, Harper ME, Love J, Botstein D. Occurrence of a transposition from the X-chromosome long arm to the Y-chromosome short arm during human evolution. Nature. 1984 Sep 13;311(5982):119–123. [PubMed]
  • Pettigrew AL, Jackson LG, Ledbetter DH. New X-linked mental retardation disorder with Dandy-Walker malformation, basal ganglia disease, and seizures. Am J Med Genet. 1991 Feb-Mar;38(2-3):200–207. [PubMed]
  • Richards RI, Shen Y, Holman K, Kozman H, Hyland VJ, Mulley JC, Sutherland GR. Fragile X syndrome: diagnosis using highly polymorphic microsatellite markers. Am J Hum Genet. 1991 Jun;48(6):1051–1057. [PMC free article] [PubMed]
  • Schwartz M, Yang HM, Niebuhr E, Rosenberg T, Page DC. Regional localization of polymorphic DNA loci on the proximal long arm of the X chromosome using deletions associated with choroideremia. Hum Genet. 1988 Feb;78(2):156–160. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Suthers GK, Callen DF, Hyland VJ, Kozman HM, Baker E, Eyre H, Harper PS, Roberts SH, Hors-Cayla MC, Davies KE, et al. A new DNA marker tightly linked to the fragile X locus (FRAXA). Science. 1989 Dec 8;246(4935):1298–1300. [PubMed]
  • Turner G, Gedeon A, Mulley J, Sutherland G, Rae J, Power K, Arthur I. Börjeson-Forssman-Lehmann syndrome: clinical manifestations and gene localization to Xq26-27. Am J Med Genet. 1989 Dec;34(4):463–469. [PubMed]
  • Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang FP, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell. 1991 May 31;65(5):905–914. [PubMed]
  • Weber JL, Kwitek AE, May PE, Polymeropoulos MH, Ledbetter S. Dinucleotide repeat polymorphisms at the DXS453, DXS454 and DXS458 loci. Nucleic Acids Res. 1990 Jul 11;18(13):4037–4037. [PMC free article] [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

  • Compound
    Compound
    PubChem Compound links
  • Gene
    Gene
    Gene links
  • MedGen
    MedGen
    Related information in MedGen
  • OMIM
    OMIM
    OMIM record citing PubMed
  • 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...