Mitochondrial analysis in autosomal dominant hereditary spastic paraplegia

Abstract

of memory deficits and behavioral changes characterized by lack of drive, loss of interest, and depression over the previous 6 months. Since the age of 36 years, she had five episodes of severe and sustained physical activity, with a sense of euphoria and intermittent irritability, followed by a period of remission or episodes of unreasonable guilt about her past acts, anxiety, and reported slowing of thought. Neuropsychological evaluation evidenced a severe overall mental decline (MMSE score 8/30). She appeared anxious and fully disoriented. Her speech was substantially reduced, with a marked impairment of verbal comprehension and closing-in phenomenon. Brain MRI scans displayed moderate atrophy of the temporal lobes.In this Italian family, the onset was characterized by an early age at onset (38.3 Ϯ 4.0 years, mean Ϯ SD) with bipolar affective symptoms and a mild memory deficit at onset. Seizures and myoclonus or extrapyramidal signs were absent. Different mutations in the same codon 392, consisting of a substitution of a Leucine (CTG) to a Valine (GTG), has been previously associated with FAD in two different families, 3,4 one of French origin and one of Italian origin. Both families with the same mutation are characterized by a very similar clinical phenotype, with memory complaints, extrapyramidal features, myoclonus and generalized seizures, and early age at onset, present in all affected members. Our observation suggests that the clinical phenotype may be different among families with different mutations in the same codon within the same hydrophilic loop of exon 11. This is a functionally important domain, which binds to a number of interacting proteins including ␤-catenin and neuronal plakophilin-related armadillo protein/␦-catenin. 5,6,7 Because this peculiar phenotype is associated with a very common mutation site, we recommend mutation screening in all FAD families with atypical features at onset.

Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia

“…We did not find functional, biochemical or morphological OXPHOS defects in two patients harbouring SPG4 mutations, in agreement with the putative nuclear localization of spastin and with previous data [23]. This is different from experimental data in the SPG7-related form.…”

NIPA1 Gene Mutations Cause Autosomal Dominant Hereditary Spastic Paraplegia (SPG6)

“…Letters refer to sequence at nucleotide 159 of the NIPA1 cDNA sequence. Clinical features (Fink et al 1995a), muscle biopsy (Hedera et al 2000 ), and genetic features (Fink et al 1995b) of ADHSP-ARK1 have been reported elsewhere. The ADHSP-IRQ1 kindred was ascertained through the University of Michigan Neurology Outpatient Clinic.…”

Surgical treatment options for spasticity in children and adolescents with hereditary spastic paraplegia

“…Below age ten, ATL1- related HSP (SPG3A) is a frequent cause of HSP. Regarding prognosis, the progression rate in this subgroup of HSP is generally slow, and wheelchair dependency or need for a walking aid (cane, walker, or wheelchair) is relatively rare [ 20 ]. In our current study, there were four children with a mutation in the ATL1 gene, of whom one was described earlier [ 13 ].…”