ABSTRACT
Objective To study the clinical characteristics and genetic cause of a Chinese family affected with paroxysmal kinesigenic dystonia(PKD).Methods The detailed clinical data and the blood samples of the affected patients with PKD and their relatives were collected.After genomic DNA was extracted from blood leukocytes,target linkage analysis Was performed using multiplex PCR by microsatellite marker's located in the reported critical region on chromosome 16.All exons and flanking regions of SCNN1G and ITGAL genes were amplified by PCR-sequence.Results In this three-generation 12 member family,5 individuals have been diagnosed as PKD.Target linkage analysis suggested the disease gene linked to chromosome 16.between D16S3396 and D16S3057 with two-point LOD score of 1.47 at recombination fraction(θ)=0.0.All affected individuals shared a common haplotype which co-segregated with the phenotype.Except for 8 reported SNPs,no pathologic sequence variants were found in candidate genes SCNN1G and ITGAL.Conclusions The studied family is genetically linked to the reported critical locus of PKD on chromosome 16.SCNN1G and ITGAL were ruled out as the causative genes for the studied pedigree.Further genetic analysis in this family may reveal new genetic cause responsible for PKD.
ABSTRACT
Objective To investigate clinical and genetic characteristics of Chinese patients with hereditary spastic paraplegia (HSP).Methods To perform retrospective analyses of clinical data from 179 HSP Han Chinese patients from Xiangya Hospital and National Laboratory of Medical Genetics of China.Results The 179 patients comprised of 114 familial cases (from 41 families with AD inheritance and 37 families with AR inheritance ) and 65 sporadic cases.Genetic anticipation was not found, and nonpenetrance was observed in some HSP families.Male to female ratio was 1.84 to 1.The mean age of onset was ( 18.1 ± 14.0) years, and the mcan duration of disease was ( 12.3 ± 11.5) years.AD-HSP patients had an older age of onset ( ( 19.7 ± 14.0) years) and a longer duration ( ( 17.9 ± 14.4) years) than ARHSP patients (t =2.196 and 4.404, P value were less than 0.05 and 0.01 respectively).Most AD patients manifested as "pure" form, while "complicated" form occurred more frequently in AR patients (F =19.322, P ＜ 0.01 ).Leg stiffness and clumsiness were often the early symptoms at the beginning of the disease, and the most common leg signs were hypertonia, hyperreflexia and pathological reflexes.Other signs included ankle clonus (46.9% ), weakness (42.5% ) and deformities (30.7% ).Ataxia, dysarthria,mental retardation, and foot deformity were more frequently seen in AR-HSP patients than AD-HSP patients,but the frequency of urinary symptoms was higher in AD-HSP patients.Among 65 patients with MRI examination of the head, 13 cases and 9 cases showed corpus callosal dysplasia and cerebellar atrophy,respectively.In addition, spinal cord atrophy was found in 7 of 45 patients undergone MRI examination of the spine.Conclusions Adolescent onset of HSP is common, and more males than females are affected.When compared with AR-HSP, AD-HSP patients have an older age of onset, a longer duration, and more marked urinary symptoms.Most AD-HSP cases are of "pure" form, while most AR-HSP cases manifest as "complicated" form with ataxia, dysarthria, and mental retardation.Dysplasia of corpus callosum is commonly seen in AR-HSP individuals than AD-HSP.HSP manifest gender-related clinical heterogeneity,illustrating the phenomenon of "female protection".