The Hereditary Spastic Paraplegias

Abstract

The hereditary spastic paraplegias (HSPs) are inherited neurologic disorders in which the primary symptom is insidiously progressive difficulty walking due to lower extremity weakness and spasticity. There have been great strides in our knowledge of this group of disabling disorders; 20 HSP loci and 9 HSP genes have been discovered. Insights into the molecular causes of HSPs are beginning to emerge. This review summarizes these advances in HSPs' genetics.

Molecular identification of ancient and modern mammalian magnesium transporters

“…Two closely related genes in this region are hNIPA1 (NM_144599) and hNIPA2 (NP_001008892). They are located in tandem on human chromosome 15q11-q13 (12,32). The corresponding mouse mNIPA1 and mNIPA2 genes are located in tandem on chromosome 7C.…”

“…HSP comprises Ͼ30 genetic disorders, the predominant feature of which is a spastic gait (32). Mutations in at least six genes, including NIPA1 (SPG6), have been associated with autosomal-dominant HSP.…”

“…In the absence of other clinical features, these disorders are referred to as pure or uncomplicated HSP (32). Fink (32) reported that uncomplicated HSP was linked to chromosome 15q, comprising NIPA1. Additional studies by this group identified a nucleotide substitution at position 134 of the NIPA1 cDNA (134C¡G, reported as 159CG) that resulted in an amino acid substitution at position 45 of the NIPA1 protein (T45R) in SPG6-linked HSP kindred (115).…”

Seipin/BSCL2 mutation screening in sporadic adult-onset upper motor neuron syndromes

“…To date, 15 genes and more than 20 additional loci have been identified for autosomal dominant (AD), autosomal recessive and X-linked forms of HSP [5,7]. The spastin gene (SPG4) mutation is the most frequent cause of AD HSP (around 40% of families) and is also frequent in sporadic HSP (13%), but not in PLS [3].…”

In-Frame Insertion Mutation in the SPG11 Gene Causes Autosomal Recessive Spastic Paraplegia with Thin Corpus Callosum “In A” Turkish Family with Late Age of Onset of the Phenotype

“…Hereditary spastic paraplegias (HSP) are a heterogeneous group of neurodegenerative disorders, in which the prominent clinical features are progressive spasticity and weakness of the lower limbs [1][2][3][4]. On the basis of clinical phenotypes, HSP can be classified into two forms: the pure and the complex HSP.…”