A novel form of juvenile recessive ALS maps to loci on 6p25 and 21q22

Abstract We describe a novel form of juvenile recessive ALS (JRALS) affecting four of six offspring from a consanguineous first cousin marriage. The syndrome is characterized by early and prominent upper motor neuron signs, along with striking amyotrophy of the upper and lower limbs and bulbar invol...

Full description

Saved in:
Bibliographic Details
Published in:Neuromuscular disorders : NMD 2009-04, Vol.19 (4), p.279-287
Main Authors: Butterfield, Russell J, Ramachandran, Deepa, Hasstedt, Sandra J, Otterud, Brith E, Leppert, Mark F, Swoboda, Kathryn J, Flanigan, Kevin M
Format: Article
Language:English
Subjects:
Adolescent
Age of Onset
Amyotrophic Lateral Sclerosis - genetics
Amyotrophic Lateral Sclerosis - pathology
Amyotrophic Lateral Sclerosis - physiopathology
Autosomal recessive ALS
Brain - pathology
Brain - physiopathology
Brain Stem - pathology
Brain Stem - physiopathology
Child
Chromosome Disorders - genetics
Chromosome Mapping
Chromosomes, Human, Pair 21 - genetics
Chromosomes, Human, Pair 6 - genetics
DNA Mutational Analysis
Genes, Recessive - genetics
Genetic Predisposition to Disease - genetics
Genetic Testing
Homozygosity mapping
Humans
Male
Motor neuron disease
Motor Neuron Disease - genetics
Motor Neuron Disease - pathology
Motor Neuron Disease - physiopathology
Mutation - genetics
Neurology
Syndrome
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract We describe a novel form of juvenile recessive ALS (JRALS) affecting four of six offspring from a consanguineous first cousin marriage. The syndrome is characterized by early and prominent upper motor neuron signs, along with striking amyotrophy of the upper and lower limbs and bulbar involvement. After excluding linkage to loci with known association to ALS and other motor neuron diseases, we used a homozygosity mapping approach to identify loci on chromosomes 6p25 and 21q22, each with an equal probability of linkage to the trait (with a LOD score = 3.1, the maximum possible given the family structure). Mutation analysis of seven candidate genes that are expressed in the CNS or have roles in neuronal function did not reveal any pathogenic mutations. Identification of additional families will help to distinguish between which of the two autosomal loci contains the disease-causing gene, or whether this is a digenic trait.
ISSN:0960-8966
1873-2364
DOI:10.1016/j.nmd.2009.02.006