Titre du document / Document title

Assignment of the disease locus for lethal congenital contracture syndrome to a restricted region of chromosome 9q34, by genome scan using five affected individuals

Auteur(s) / Author(s)

MÄKELÄ-BENGS P. ⁽¹⁾ ; JÄRVINEN N. ⁽²⁾ ; VUOPALA K. ^{(3 4)} ; SUOMALAINEN A. ⁽¹⁾ ; IGNATIUS J. ⁽⁵⁾ ; SIPILÄ M. ⁽¹⁾ ; HERVA R. ⁽⁴⁾ ; PALOTIE A. ⁽²⁾ ; PELTONEN L. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Human Molecular Genetics, National Public Health Institute, and Department of Medical Genetics, University of Helsinki, Helsinki, FINLANDE
⁽²⁾ Department of Clinical Chemistry, University of Helsinki, Helsinki, FINLANDE
⁽³⁾ Department of Pathology, Lapland Central Hospital, Rovaniemi, FINLANDE
⁽⁴⁾ Department of Pathology, University of Oulu, Oulu, FINLANDE
⁽⁵⁾ Department of Clinical Neurophysiology, Jorvi Hospital, Espoo, FINLANDE

Résumé / Abstract

Lethal congenital contracture syndrome (LCCS) is an autosomal recessive disease leading to death before the 32d gestational week. It is characterized by the fetal akinesia phenotype, with highly focused degeneration of motoneurons in the spinal cord as the main neuropathological finding. We report here the assignment of the LCCS locus to a defined region of chromosome 9q34, between markers D9S1825 and D9S1830. The initial genome scan was performed with the DNA samples of only five affected individuals from two unrelated LCCS families. The conventional linkage analysis performed with 20 affected individuals and their families was focused on those chromosomal regions in which the affected siblings were identical by descent in the initial scan. One core haplotype of 3 cM was observed in LCCS alleles, supporting the assumption of one major mutation underlying LCCS, and linkage disequilibrium analysis restricted the critical chromosomal region to <100 kb in the vicinity of marker D9S61. Two genes, NGAL (neutrophil gelatinase-associated lipocalin and NOTCH 1, were excluded as causative genes for LCCS

Revue / Journal Title

American journal of human genetics   ISSN 0002-9297   CODEN AJHGAG 

Source / Source

1998, vol. 63, n^o2, pp. 506-516 (1 p.1/4)

Langue / Language

Anglais

Editeur / Publisher

University of Chicago Press, Chicago, IL, ETATS-UNIS  (1949) (Revue)

Mots-clés anglais / English Keywords

Contracture ; Muscle ; Lethal character ; Akinesia ; Fetus ; Human ; Degeneration ; Motor neuron ; Chromosome C9 ; Locus ; Genetic determinism ; Family study ; Linkage ; Genetic mapping ; Linkage equilibrium ; Pathogenesis ; Striated muscle disease ; Congenital disease ; Genetic disease ; Genetics ; Molecular biology ; Fetal diseases ; Nervous system diseases ; Central nervous system disease ; Cerebral disorder ; Neurological disorder ; Motor system disorder ;

Mots-clés français / French Keywords

Contracture ; Muscle ; Caractère létal ; Akinésie ; Foetus ; Homme ; Dégénérescence ; Neurone moteur ; Chromosome C9 ; Locus ; Déterminisme génétique ; Etude familiale ; Liaison génétique ; Carte génétique ; Equilibre linkage ; Pathogénie ; Muscle strié pathologie ; Maladie congénitale ; Maladie héréditaire ; Génétique ; Biologie moléculaire ; Foetus pathologie ; Système nerveux pathologie ; Système nerveux central pathologie ; Encéphale pathologie ; Trouble neurologique ; Trouble moteur ;

Mots-clés espagnols / Spanish Keywords

Contractura ; Músculo ; Carácter letal ; Aquinesia ; Feto ; Hombre ; Degeneración ; Neurona motora ; Cromosoma C9 ; Locus ; Determinismo genético ; Estudio familiar ; Ligamiento genético ; Mapa genético ; Equilibrio ligazón ; Patogenia ; Músculo estriado patología ; Enfermedad congénita ; Enfermedad hereditaria ; Genética ; Biología molecular ; Feto patología ; Sistema nervioso patología ; Sistema nervosio central patología ; Encéfalo patología ; Trastorno neurológico ; Trastorno motor ;

Localisation / Location

INIST-CNRS, Cote INIST : 2610, 35400007021620.0250