# 614373
AMYOTROPHIC LATERAL SCLEROSIS 16, JUVENILE; ALS16
ORPHA: 300605; DO: 0060207;
Phenotype-Gene Relationships
| Location | Phenotype | Phenotype MIM number |
Inheritance | Phenotype mapping key |
Gene/Locus | Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 9p13.3 | ?Amyotrophic lateral sclerosis 16, juvenile | 614373 | Autosomal recessive | 3 | SIGMAR1 | 601978 |
TEXT
A number sign (#) is used with this entry because of evidence that juvenile amyotrophic lateral sclerosis-16 (ALS16) is caused by homozygous mutation in the SIGMAR1 gene (601978) on chromosome 9p13. One such family has been reported.
Clinical Features
Al-Saif et al. (2011) reported a consanguineous Saudi Arabian family in which 6 individuals had early-childhood onset of a neurologic disorder consistent with juvenile ALS, according to the El Escorial criteria (Brooks, 1994). Lower limb spasticity with hyperreflexia and weakness were noted at the age of 1 to 2 years. By age 9 or 10, affected individuals showed weakness of the hand and forearm muscles, which progressed to paralysis of the forearm extensors and triceps. By the age of 20 years, 2 patients used wheelchairs. None of the patients had respiratory or bulbar muscle weakness, and sensory and cerebellar functions were normal. Neurophysiologic tests showed evidence of denervation and reinnervation in limb muscles; motor unit potentials were enlarged, polyphasic, and fast firing, with normal sensory nerve action potentials and somatosensory evoked potentials. Brain imaging did not reveal any abnormalities, and cognition was preserved.
Mapping
By homozygosity mapping of a consanguineous Saudi Arabian family with early-childhood onset of ALS, Al-Saif et al. (2011) found linkage to a 120-kb region on chromosome 9p13.3.
Molecular Genetics
By homozygosity mapping followed by candidate gene sequencing, Al-Saif et al. (2011) identified a homozygous pathogenic mutation in the SIGMAR1 gene (601978.0001) in affected members of a consanguineous Saudi Arabian family with early-childhood onset of ALS.
REFERENCES
-
Al-Saif, A., Al-Mohanna, F., Bohlega, S. A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Ann. Neurol. 70: 913-919, 2011. [PubMed: 21842496] [Full Text: https://doi.org/10.1002/ana.22534]
-
Brooks, B. R. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial 'Clinical limits of amyotrophic lateral sclerosis' workshop contributors. J. Neurol. Sci. 124 Suppl.: 96-107, 1994. [PubMed: 7807156] [Full Text: https://linkinghub.elsevier.com/retrieve/pii/0022-510X(94)90191-0]
terry : 7/5/2012
carol : 12/8/2011
ckniffin : 12/8/2011