Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0700208 (
scoliosis
)
8,574
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mutations in SPG4/
SPAST
are the most frequent molecular aetiology in the autosomal dominant form of hereditary spastic paraplegia (HSP). Loss-of-function and haploinsufficiency in
SPAST
have been demonstrated and the pure form of spastic paraplegia is a main clinical manifestation. This study is to explore the novel
SPAST
splice site donor variant, c.1004+3A>C, in seven patients from two families, one from Italy and the other from Japan. Exon 6 is skipped out by the variant, leading to a premature termination of translation, p.Gly290Trpfs*5. Measurement of
SPAST
transcripts in lymphocytes demonstrated a reduction through nonsense-mediated mRNA decay (NMD). Intra- and inter-familial phenotypic variations were observed, including age-at-onset, severity of spasticity, and
scoliosis
. Our study demonstrated further evidence of allelic heterogeneity in SPG4, dosage effects through NMD, and broad clinical features of the
SPAST
mutation.
...
PMID:Spastic paraplegia type 4: A novel SPAST splice site donor mutation and expansion of the phenotype variability. 2887 May 97
