neurogenetics

, Volume 12, Issue 1, pp 73–78

A whole-genome scan in a large family with leukodystrophy and oligodontia reveals linkage to 10q22

  • Eliane Chouery
  • Valérie Delague
  • Nadine Jalkh
  • Nabiha Salem
  • Jessy Kfoury
  • Diana Rodriguez
  • Brigitte Chabrol
  • Odile Boespflug-Tanguy
  • Nicolas Lévy
  • Jean Louis Serre
  • André Mégarbané
ORIGINAL ARTICLE

DOI: 10.1007/s10048-010-0256-3

Cite this article as:
Chouery, E., Delague, V., Jalkh, N. et al. Neurogenetics (2011) 12: 73. doi:10.1007/s10048-010-0256-3

Abstract

Dentoleukoencephalopathies with autosomal recessive inheritance are very rare. Recently, a large inbred Syrian pedigree was reported with oligodontia in association with a degenerative neurologic condition characterized by progressive ataxia and pyramidal syndrome and abnormalities in the white matter and cortical atrophy. A whole-genome screening of this family using 382 microsatellite markers was completed, but no evidence was found of linkage to any chromosomal region. A genome-wide linkage analysis using the 260K single nucleotide polymorphism Affymetrix array was then undertaken and a maximum multipoint logarithm of the odds score of 5.66 (NPL score = 7.65) was detected on chromosome 10q22 region. This genomic interval contains 95 known genes including the Prosaposin gene (PSAP) responsible for metachromatic leukodystrophy, which was excluded. Seventeen additional candidate genes were tested and excluded. Sequencing of the whole candidate locus is in progress and should allow the identification of the causative gene in this rare disease, thereby improving the understanding of the physiopathology of this disease.

Keywords

Leukodystrophy Oligodontia Linkage analysis Microsatellite markers SNP markers 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Eliane Chouery
    • 1
  • Valérie Delague
    • 2
  • Nadine Jalkh
    • 1
  • Nabiha Salem
    • 1
  • Jessy Kfoury
    • 1
  • Diana Rodriguez
    • 3
    • 9
  • Brigitte Chabrol
    • 4
  • Odile Boespflug-Tanguy
    • 5
  • Nicolas Lévy
    • 2
  • Jean Louis Serre
    • 6
  • André Mégarbané
    • 1
    • 7
    • 8
  1. 1.Unité de Génétique Médicale et laboratoire associé INSERM à l’unité UMR_S 910, Faculté de MédecineUniversité Saint-JosephBeirutLebanon
  2. 2.«Génétique Médicale et Génomique Fonctionnelle» Faculté de Médecine de la TimoneINSERM UMR_S 910MarseilleFrance
  3. 3.Service de neuro-pédiatrieHôpital TrousseauParisFrance
  4. 4.Service de neurologie pédiatriqueCHU La-TimoneMarseilleFrance
  5. 5.Service de Neurologie Pédiatrique et des Maladies MétaboliquesHôpital Robert DebréParisFrance
  6. 6.Université de Versailles-Saint Quentin en YvelinesVersaillesFrance
  7. 7.Institut Jérôme LejeuneParisFrance
  8. 8.Unité de Génétique Médicale, Faculté de MédecineUniversité Saint-Joseph 42ParisFrance
  9. 9.UPMC Université Paris 06ParisFrance