Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Troyer syndrome was found by Cross & McKusick (1967) in 20 members of 12 Old Order Amish families in Holmes County, Ohio; it is a form of hereditary spastic paraplegia combined with distal muscle wasting, i.e. signs of involvement of lower motor neurons. The condition usually begins at 1 to 2 years and progresses at variable rates. Further manifestations include growth retardation, delayed speech development with dysarthria and drooling, and cerebellar signs; mental functions are usually not affected but severe emotional lability is a common finding. Brothers in a Wisconsin Old Order Amish family are reported with spastic diplegia, mental retardation, behavioral disorder and shortness of stature; the condition apparently is not progressive, and may be a "new" syndrome but could also represent a variant of the Troyer syndrome. Autosomal recessive inheritance is most likely, although consanguinity of the parents could not be proven. Another child in this family suffers from focal scleroderma (morphea) which is not related to the neurological syndrome.
 ...
PMID:Familial spastic paraplegia with distal muscle wasting in the Old Order Amish; atypical Troyer syndrome or "new" syndrome. 126 Oct 70

Hereditary spastic paraplegia is a group of clinically and genetically heterogeneous disorders consisting of pure and complicated forms. A variant with the additional features of severe atrophy of the small hand muscles, dysarthria, mental retardation, and short stature has been termed Troyer syndrome (MIM#275900) after the name of Old Order Amish families suffering from these symptoms. We report here an Austrian family with two individuals who exhibit all the features of Troyer syndrome, and provide additional data on this disorder. Electrophysiological studies showed chronic denervation and reduced motor nerve conduction velocities but normal sensory potentials. Muscle biopsy revealed a neurogenic pattern while the sural nerve was normal on histological examination. Brain abnormalities on magnetic resonance imaging consisted of a thin corpus callosum with a poorly developed cingulate gyrus and mild periventricular signal hyperintensities. These findings characterize the Troyer syndrome as a disorder of the first and second motor neuron with additional damage in the brain. The morphological features observed in this family may contribute to the grouping and subsequent understanding of complicated forms of hereditary spastic paraplegia, together with similar observations in other, more recently reported families.
 ...
PMID:Troyer syndrome: a combination of central brain abnormality and motor neuron disease? 1046 56

Hereditary spastic paraplegia describes a diverse group of disorders characterized by progressive paraparesis primarily affecting lower limbs. In Troyer syndrome, an autosomal recessive form of hereditary spastic paraplegia, patients have dysarthria, distal amyotrophy, developmental delay and short stature in addition to spastic paraparesis. It is caused by a frameshift mutation (1110delA) in SPG20 leading to premature truncation of spartin, a protein with no known function. The objective of this study was to determine the subcellular localization of spartin and investigate the effect of the 1110delA mutation. We observed cytoplasmic expression of spartin in all transfected cell lines. Using superimposed organelle markers or immunocytochemistry staining, we established that spartin localizes to mitochondria and that this localization is dependent on sequences in the C-terminal region. Mutant spartin containing the 1110delA mutation has lost mitochondrial localization. Immunocytochemistry staining using anti-alpha-tubulin antibody provided evidence for partial co-localization of spartin with microtubules. Analysis of fluorescence resonance energy transfer indicated that sequences in the amino terminal are important in mediating microtubule interaction. This study provides the first evidence of spartin subcellular localization and identifies it as the third mitochondrial protein implicated in hereditary spastic paraplegia. Our results suggest that Troyer syndrome may be due to defective microtubule-mediated trafficking of mitochondria and/or mitochondrial dysfunction.
 ...
PMID:The hereditary spastic paraplegia protein spartin localises to mitochondria. 1694 7

Troyer syndrome is an autosomal recessive form of hereditary spastic paraplegia (HSP) caused by deleterious mutations in the SPG20 gene. Although the disease is associated with a loss of function mechanism of spartin, the protein encoded by SPG20, the precise pathogenesis is yet to be elucidated. Recent data indicated an important role for spartin in both mitochondrial maintenance and function. Here we report a child presenting with progressive spastic paraparesis, generalized muscle weakness, dysarthria, impaired growth, and severe isolated decrease in muscle cytochrome c oxidase (COX) activity. Whole exome sequencing identified the homozygous c.988A>G variant in SPG20 gene (p.Met330Val) resulting in almost complete loss of spartin in skeletal muscle. Further analyses demonstrated significant tissue specific reduction of COX 4, a nuclear encoded subunit of COX, in muscle suggesting a role for spartin in proper mitochondrial respiratory chain function mediated by COX activity. Our findings need to be verified in other Troyer syndrome patients in order to classify it as a form of HSP caused by mitochondrial dysfunction.
 ...
PMID:Novel Homozygous Missense Mutation in SPG20 Gene Results in Troyer Syndrome Associated with Mitochondrial Cytochrome c Oxidase Deficiency. 2753 78

Troyer syndrome (MIM#275900) is an autosomal recessive form of complicated hereditary spastic paraplegia. It is characterized by progressive lower extremity spasticity and weakness, dysarthria, distal amyotrophy, developmental delay, short stature, and subtle skeletal abnormalities. It is caused by deleterious mutations in the SPG20 gene, encoding spartin, on Chromosome 13q13. Until now, six unrelated families with a genetically confirmed diagnosis have been reported. Here we report the clinical findings in three brothers of a consanguineous Moroccan family, aged 24, 17, and 7 yr old, with spastic paraplegia, short stature, motor and cognitive delay, and severe intellectual disability. Targeted exon capture and sequencing showed a homozygous nonsense mutation in the SPG20 gene, c.1369C>T (p.Arg457*), in the three affected boys.
 ...
PMID:SPG20 mutation in three siblings with familial hereditary spastic paraplegia. 2867 90

Troyer syndrome is an autosomal recessive disease characterized by spastic paralysis, dysarthria, distal amyotrophy, and short stature. Recently, two siblings (an older brother and a younger sister) were admitted to our hospital for the chief complaints of "short stature and intellectual disability." Through whole exome sequencing of the sister, who is the proband, it was found that her SPG20 gene had compound heterozygous mutations: c.364_365delAT (p.Met122Valfs* 2) and c.892delA (p.Thr298Glnfs* 30). Target testing revealed that the brother had the same genotype as the sister, and the former mutation originated from the father, while the latter mutation originated from the mother. In summary, this is the first report of Troyer syndrome in a family caused by SPG20 compound heterozygous mutations. A novel SPG20 mutation was found, namely c.892delA (p.Thr298Glnfs* 30). In addition, we also summarize these Troyer syndrome patients' heights and their clinical characteristics, and provide a brief review of all known pathogenic mutations of SPG20.
 ...
PMID:Dwarfism in Troyer syndrome: a family with SPG20 compound heterozygous mutations and a literature review. 3153 23