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Genotype-phenotype relationship in hereditary amyotrophic lateral sclerosis.

Yamashita S, Ando Y - Transl Neurodegener (2015)

Bottom Line: Thus, genetic factors play a role in all types of ALS, to a greater or lesser extent.During the decade of upheaval, the evolution of molecular genetics technology has rapidly advanced our genetic knowledge about the causes of ALS, and the relationship between the genetic subtypes and clinical phenotype.Uncovering the identity of the genetic factors in ALS will not only improve the accuracy of ALS diagnosis, but may also provide new approaches for preventing and treating the disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 Japan.

ABSTRACT
Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. It is characterized by neuronal loss and degeneration of the upper motor neurons (UMNs) and lower motor neurons (LMNs), and is usually fatal due to respiratory failure within 3-5 years of onset. Although approximately 5-10 % of patients with ALS have an inherited form of the disease, the distinction between hereditary and apparently sporadic ALS (SALS) seems to be artificial. Thus, genetic factors play a role in all types of ALS, to a greater or lesser extent. During the decade of upheaval, the evolution of molecular genetics technology has rapidly advanced our genetic knowledge about the causes of ALS, and the relationship between the genetic subtypes and clinical phenotype. In this review, we will focus on the possible genotype-phenotype correlation in hereditary ALS. Uncovering the identity of the genetic factors in ALS will not only improve the accuracy of ALS diagnosis, but may also provide new approaches for preventing and treating the disease.

No MeSH data available.


Related in: MedlinePlus

Flowchart for diagnosis of hereditary juvenile-onset ALS
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Fig3: Flowchart for diagnosis of hereditary juvenile-onset ALS

Mentions: We describe the possible correlation between the genotype and phenotype, and aim to provide a clue to the diagnosis of ALS. ALS cases can be divided into 3 groups: juvenile onset less than 10 years or less 25 years, and adult onset type. Cases with juvenile onset were categorized into 2 groups because we could differentiate the genes that cause juvenile ALS alone from the genes that cause both juvenile and adult-onset ALS. ALS cases with juvenile onset less than 10 years include cases with mutations in the SPG11, Alsin, SETX, and SIGMAR1 genes (Fig. 3). When the symptoms are UMN-dominant, SPG and Alsin can be causative genes for ALS. In contrast, SETX might be responsible in cases with LMN-dominant symptoms such as PMA type. In ALS cases with onset from 10 to 24 years, SPG11, FUS, VAPB, SOD1, SETX, ATXN2, ANG, and UBQLN2 should be considered as a cause of ALS (Fig. 3). SPG or UBQLN2 might be a causative gene in UMN-dominant cases whereas FUS, VAPB, SOD1, and SETX should be examined in LMN-dominant cases.Fig. 3


Genotype-phenotype relationship in hereditary amyotrophic lateral sclerosis.

Yamashita S, Ando Y - Transl Neurodegener (2015)

Flowchart for diagnosis of hereditary juvenile-onset ALS
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4513711&req=5

Fig3: Flowchart for diagnosis of hereditary juvenile-onset ALS
Mentions: We describe the possible correlation between the genotype and phenotype, and aim to provide a clue to the diagnosis of ALS. ALS cases can be divided into 3 groups: juvenile onset less than 10 years or less 25 years, and adult onset type. Cases with juvenile onset were categorized into 2 groups because we could differentiate the genes that cause juvenile ALS alone from the genes that cause both juvenile and adult-onset ALS. ALS cases with juvenile onset less than 10 years include cases with mutations in the SPG11, Alsin, SETX, and SIGMAR1 genes (Fig. 3). When the symptoms are UMN-dominant, SPG and Alsin can be causative genes for ALS. In contrast, SETX might be responsible in cases with LMN-dominant symptoms such as PMA type. In ALS cases with onset from 10 to 24 years, SPG11, FUS, VAPB, SOD1, SETX, ATXN2, ANG, and UBQLN2 should be considered as a cause of ALS (Fig. 3). SPG or UBQLN2 might be a causative gene in UMN-dominant cases whereas FUS, VAPB, SOD1, and SETX should be examined in LMN-dominant cases.Fig. 3

Bottom Line: Thus, genetic factors play a role in all types of ALS, to a greater or lesser extent.During the decade of upheaval, the evolution of molecular genetics technology has rapidly advanced our genetic knowledge about the causes of ALS, and the relationship between the genetic subtypes and clinical phenotype.Uncovering the identity of the genetic factors in ALS will not only improve the accuracy of ALS diagnosis, but may also provide new approaches for preventing and treating the disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 Japan.

ABSTRACT
Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. It is characterized by neuronal loss and degeneration of the upper motor neurons (UMNs) and lower motor neurons (LMNs), and is usually fatal due to respiratory failure within 3-5 years of onset. Although approximately 5-10 % of patients with ALS have an inherited form of the disease, the distinction between hereditary and apparently sporadic ALS (SALS) seems to be artificial. Thus, genetic factors play a role in all types of ALS, to a greater or lesser extent. During the decade of upheaval, the evolution of molecular genetics technology has rapidly advanced our genetic knowledge about the causes of ALS, and the relationship between the genetic subtypes and clinical phenotype. In this review, we will focus on the possible genotype-phenotype correlation in hereditary ALS. Uncovering the identity of the genetic factors in ALS will not only improve the accuracy of ALS diagnosis, but may also provide new approaches for preventing and treating the disease.

No MeSH data available.


Related in: MedlinePlus