#612577
Table of Contents
- Prominent corticospinal tract pathology [UMLS: C4314906]
- Denervation seen on EMG [UMLS: C3809981]
- Pseudobulbar affect [SNOMEDCT: 432776007] [ICD10CM: F48.2] [ICD9CM: 310.81] [UMLS: C2316460]
▼ TEXT
A number sign (#) is used with this entry because this form of autosomal dominant ALS is caused by mutation in the FIG4 gene (609390).
Autosomal recessive Charcot-Marie Tooth disease type 4J (CMT4J; 611228) is an allelic disorder with a much more severe phenotype.
For a general phenotypic description and a discussion of genetic heterogeneity of amyotrophic lateral sclerosis (ALS), see ALS1 (105400).
Chow et al. (2009) reported 5 unrelated patients diagnosed with probable or definite ALS. Two had a family history of the disorder. All had adult onset and showed prominent corticospinal tract findings. Nerve conduction velocity studies were normal, but EMG studies showed some denervation.
In 5 unrelated patients with amyotrophic lateral sclerosis, Chow et al. (2009) identified heterozygosity for a missense, 2 splice site, and 2 truncating mutations in the FIG4 gene (see, e.g., 609390.0006-609390.0008). The mutations were shown to result in complete or highly significant loss of protein function. Five different missense FIG4 mutations were identified in 5 patients with a diagnosis of ALS or adult-onset primary lateral sclerosis (PLSA1; 611637), but these mutations were not clearly shown to be pathogenic.
▼ REFERENCES
-
Chow, C. Y., Landers, J. E., Bergren, S. K., Sapp, P. C., Grant, A. E., Jones, J. M., Everett, L., Lenk, G. M., McKenna-Yasek, D. M., Weisman, L. S., Figlewicz, D., Brown, R. H., Meisler, M. H. Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. Am. J. Hum. Genet. 84: 85-88, 2009. [PubMed: 19118816, related citations] [Full Text]
# 612577
AMYOTROPHIC LATERAL SCLEROSIS 11; ALS11
ORPHA: 803; DO: 0060202;
Phenotype-Gene Relationships
| Location | Phenotype | Phenotype MIM number |
Inheritance | Phenotype mapping key |
Gene/Locus | Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 6q21 | Amyotrophic lateral sclerosis 11 | 612577 | Autosomal dominant | 3 | FIG4 | 609390 |
TEXT
A number sign (#) is used with this entry because this form of autosomal dominant ALS is caused by mutation in the FIG4 gene (609390).
Autosomal recessive Charcot-Marie Tooth disease type 4J (CMT4J; 611228) is an allelic disorder with a much more severe phenotype.
For a general phenotypic description and a discussion of genetic heterogeneity of amyotrophic lateral sclerosis (ALS), see ALS1 (105400).
Clinical Features
Chow et al. (2009) reported 5 unrelated patients diagnosed with probable or definite ALS. Two had a family history of the disorder. All had adult onset and showed prominent corticospinal tract findings. Nerve conduction velocity studies were normal, but EMG studies showed some denervation.
Molecular Genetics
In 5 unrelated patients with amyotrophic lateral sclerosis, Chow et al. (2009) identified heterozygosity for a missense, 2 splice site, and 2 truncating mutations in the FIG4 gene (see, e.g., 609390.0006-609390.0008). The mutations were shown to result in complete or highly significant loss of protein function. Five different missense FIG4 mutations were identified in 5 patients with a diagnosis of ALS or adult-onset primary lateral sclerosis (PLSA1; 611637), but these mutations were not clearly shown to be pathogenic.
REFERENCES
-
Chow, C. Y., Landers, J. E., Bergren, S. K., Sapp, P. C., Grant, A. E., Jones, J. M., Everett, L., Lenk, G. M., McKenna-Yasek, D. M., Weisman, L. S., Figlewicz, D., Brown, R. H., Meisler, M. H. Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. Am. J. Hum. Genet. 84: 85-88, 2009. [PubMed: 19118816] [Full Text: https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(08)00631-9]
ckniffin : 2/3/2009