A gene for an autosomal recessive lower motor neuron disease with childhood onset maps to 1p36.
OBJECTIVE
To describe the clinical features of a novel variant of autosomal recessive lower motor neuron disease (LMND) with childhood onset and to map the disease-causing gene.


METHODS
The authors performed a clinical study in a large consanguineous African family. After linkage exclusion to SMN1 and SOD1 loci, they performed a genome-wide linkage analysis to map the underlying genetic defect.


RESULTS
This novel variant of LMND with childhood onset and autosomal recessive mode of inheritance is characterized by a progressive symmetric and generalized involvement of the musculature. Four of the five affected patients had muscle weakness since age 3, strongly worsening during childhood and leading to generalized tetraplegia in adulthood. Genetic analyses using homozygosity mapping strategy assigned this progressive generalized LMND locus to an interval of 3.9 cM (or 1.5 megabases) on chromosome 1p36, between loci D1S508 and D1S2633 (Z(max) = 3.79 at theta = 0.00 at locus D1S253). This region encloses 27 candidate genes.


CONCLUSIONS
Genetic mapping of a novel rare phenotype of lower motor neuron disease opens the way toward the identification of a new gene involved in motor neuron degeneration, located in the 1p36 chromosomal region.
Maystadt
I
I
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker Enfants Malades, 149 rue de Sèvres, F-75743 Paris Cedex 15, France.
Zarhrate
M
M
Leclair-Richard
D
D
Estournet
B
B
Barois
A
A
Renault
F
F
Routon
M-C
MC
Durand
M-C
MC
Lefebvre
S
S
Munnich
A
A
Verellen-Dumoulin
C
C
Viollet
L
L
D000293:Adolescent; D000328:Adult; D002648:Child; D002874:Chromosome Mapping / Q000379:methods; D002878:Chromosomes, Human, Pair 1; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D016472:Motor Neuron Disease / Q000235:genetics*