The hereditary spastic paraplegia (HSP) is a rare hereditary disease in nervous system due to the damage of corticospinal tract. HSP has various inheritance modes, including autosomal dominant inheritance, autosomal recessive inheritance, X-linked inheritance, and mitochondrial inheritance in some cases. At present, there are at least 80 subtypes of HSP. Hereditary spastic paraplegia type 11 (SPG11) is the most common subtype in autosomal recessive inheritance, and its pathogenic factor is KIAA1840 gene, which encodes spatacsin protein. A total of 52 SPG11 patients aged from 4-24 years old have been reported. Their initial symptoms were gait disturbance and/or mental retardation. As the disease develops, they may present with mental retardation, sphincter disturbance, decreased vision, ataxia, amyotrophy, pes arcuatus, ophthalmoplegia, peripheral neuropathy, and others. Except agenesis of the corpus callosum and periventricular white matter changes, patients might show cortical atrophy, ventricular dilation, and cerebellar atrophy, and so on. Chinese SPG11 patients manifested significant clinical and genetical heterogeneity and no obvious gender difference. Of them, 37 pathogenic mutations of KIAA1840 gene were detected, which all introduced truncated mutation of spatacsin protein. KIAA1840 gene frameshift mutation is the most common type of mutation.
Adolescent ; Child ; Child, Preschool ; Humans ; Young Adult ; Atrophy ; Intellectual Disability ; Mutation ; Proteins ; Spastic Paraplegia, Hereditary/pathology*

The hereditary spastic paraplegia (HSP), also known as Strumpell-Lorrain familial spasmodic paraplegia, is a highlighted clinical and genetic heterogeneity disorder with the prevalence of (2-9.6)/100,000. This disorder is characterized by progressive, usually severe spasticity and pyramidal weakness, predominantly in the lower limbs. Inheritance of this disease has been reported to be autosomal dominant (AD), autosomal recessive (AR), or X-linked recessive (XR), with the AD forms of HSP (ADHSP) being the most common type. At least 40 HSP gene loci have been localized and 19 genes have been identified. Forty percent of HSP cases are caused by mutations in the spastin (spastic paraplegia-4, SPG4) gene. Genetic diagnosis, the gold standard for diagnosis of the disease, may contribute to early diagnosis, presymptomatic diagnosis and prenatal diagnosis. The study of animal models plays an important role in revealing the molecular pathological mechanism of HSP. The known genetic research advances of the SPG4 gene are reviewed in this article.
Adenosine Triphosphatases ; genetics ; Animals ; Humans ; Spastic Paraplegia, Hereditary ; diagnosis ; genetics ; pathology ; Spastin

OBJECTIVETo describe the clinical features of a big family with incompletely penetrated autosomal dominant hereditary spastic paraplegia (SPG) and perform the exclusion analysis of genetic loci.

METHODSThe clinical information of this SPG family was analyzed retrospectively. Exclusion analysis of the known autosomal dominant SPG loci was performed by using multiplex fluorescence PCR, capillary electrophoresis and Linkage package.

RESULTSThere were eleven affected members available in this SPG family and the age at onset ranged from 2 to 10 years. The first symptoms were a bilateral, symmetrical, progressive lower limb weakness and spasticity. Patients presented with spasticity and hyperreflexia, positive Babinski sign and scissors gait, and the upper limbs were involved more severely than the lower limbs. No urinary inconsistence, sensory impairment, nystagmus and dementia were found. Genetic analysis showed that this family was consistent with autosomal dominant inheritance. The linkage analysis and mutation analysis revealed this family was not linked to the known autosomal dominant loci.

CONCLUSIONThis SPG family had typical "pure" clinical symptoms. The age at onset was early and the signs in the upper limbs were more obvious than those in the lower limbs. The result of linkage analysis shows that this family represents a new SPG subtype.

Female ; Genetic Linkage ; genetics ; Humans ; Male ; Pedigree ; Spastic Paraplegia, Hereditary ; genetics ; pathology

OBJECTIVETo investigate the clinical characteristics and analyze spastin gene mutation on a kindred with hereditary spastic paraplegia (HSP).

METHODSAll family members were studied through clinical examinations. The proband and another two patients in this kindred were subjected to electromyography (EMG) examinations. The proband was subjected to thoracic MRI examination too. Mutation analysis of spastin gene was screened by polymerase chain reaction combined with DNA sequencing in the proband and his father.

RESULTSAll patients in the kindred manifested as classical HSP. Thoracic MRI revealed atrophies of the spinal cord in the proband. No abnormal spastin gene mutation was detected in these two patients.

CONCLUSIONThis kindred has typical clinical manifestations of HSP. The pathogenesis has no association with mutation of the exons of spastin gene.

Adenosine Triphosphatases ; genetics ; Adult ; Aged ; Aged, 80 and over ; Base Sequence ; DNA Mutational Analysis ; Electromyography ; Exons ; genetics ; Family Health ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Mutation ; Pedigree ; Polymerase Chain Reaction ; Spastic Paraplegia, Hereditary ; genetics ; pathology ; Spastin ; Young Adult

OBJECTIVETo screen all ten genes between D15S971 and D15S1012 in five Chinese families with hereditary spastic paraplegia with thin corpus callosum (HSP-TCC).

METHODSDNA samples from 5 HSP-TCC families were screened for mutations in AK128197, MGC14798, HH114, MEIS2, MGC35118, SPRED1, AK128458, FLJ38426, RASGRP1 and AK093014 on chromosome 15q13-15 between microsatellites D15S971 and D15S1012 by polymerase chain reaction, direct sequencing and cosegreagation analysis.

RESULTSNo disease-causing mutations were found in the 10 genes, but 13 polymorphisms were identified in which two were novel.

CONCLUSIONThis study did not support the ten genes between D15S971 and D15S1012 were the disease-causing genes of the 5 HSP-TCC families.

Adult ; Asian Continental Ancestry Group ; genetics ; Chromosomes, Human, Pair 15 ; Corpus Callosum ; pathology ; Female ; Genes, Recessive ; Humans ; Male ; Paraparesis, Spastic ; genetics ; Spastic Paraplegia, Hereditary ; complications ; genetics

BACKGROUNDHereditary spastic paraplegia is a clinically and genetically heterogeneous group of neurodegenerative disorders of the motor system, characterized by slowly progressive spasticity and weakness of the lower extremities. This study was conducted to investigate the clinical features of hereditary spastic paraplegia with thin corpus callosum (HSP-TCC).

METHODSClinical data from five patients and thirty-five previously published case reports of HSP-TCC were analyzed retrospectively.

RESULTSMost patients were adolescents at the onset of the disease, presenting with spastic paraparesis of the lower limbs and mental impairment. Some patients also had other clinical features, including spasticity of the upper limbs, cerebellar ataxia, and sensory disturbances. Cranial MRIs of the five patients revealed an extremely thin corpus callosum, sometimes with widened cerebral sulci and ventricles, as well as with cerebellar and cerebral atrophy.

CONCLUSIONThe main clinical features of HSP-TCC include slowly progressive spastic paraplegia, mental impairment during the second decade of life, and an extremely thin corpus callosum as shown on cranial MRIs.

Adolescent ; Adult ; Agenesis of Corpus Callosum ; Chromosomes, Human, Pair 15 ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Spastic Paraplegia, Hereditary ; genetics ; pathology