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GENATLAS PHENOTYPE

last update : 08-10-2013

Symbol	SPG4
Location	2p22.3
Name	spastic paraplegia 4
Corresponding gene	SPAST
Other symbol(s)	HSP, FSP2
Main clinical features	Strumpell-Lorrain type, most common, pure and complicated form onset in infancy through senescence associated with late cognitive impairment, active progression of cognitive deterioration and dementia in older patients, epilepsy cases with infantile onset of spastic paraplegia mimicking infantile cerebral palsy (Blair 2007)
Genetic determination	autosomal dominant
Prevalence	up to 40p 100 of autosomal dominant hereditary spastic paraplegia
Function/system disorder	neurology
Type	disease

Gene product

Name

spastin

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments
missense			1375A > G (R459G) and 1378C > T (R460C)
other			mostly non recurrent mutations affecting the AAA cassette
deletion		haploinsufficiency
various types		abnormal protein/gain of function

Remark(s)

. clustering was observed in the AAA (ATPases associated with diverse cellular activities) domain (Shoukier 2009)

Genotype/Phenotype correlations

age at onset significantly earlier in microdeletion multi-exonic duplication (exon10_12dup), leading to a premature stop codon, with protein product not functional and males have on average an earlier age at onset and are more severely affected missense mutations could cause an earlier onset of the disease (Shoukier 2009) cognitive decline and dementia is a feature of SPG4 due to a deletion of exon 17 of the spastin gene (PMID: 19652142))