Adolescent idiopathic scoliosis (AIS) is one of the most common orthopedic disorders, affecting up to 4% of schoolchildren worldwide. We studied seven unrelated multiplex families of southern Chinese descent with AIS, consisting of 25 affected members. A genomewide scan with >400 fluorescent microsatellite markers was performed. Multipoint linkage analysis by GENEHUNTER revealed significant linkage of the abnormal phenotype to the distal short arm of chromosome 19, with both a maximum multipoint LOD score and a nonparametric LOD score of 4.93. Two-point linkage analysis by MLINK gave a LOD score of 3.63 (recombination fraction theta[m=f]=0.00) at D19S216. Further high-density mapping and informative recombinations defined the AIS critical region in the vicinity of D19S216, flanked by D19S894 and D19S1034, spanning 5.2 cM on the sex-averaged genetic map on chromosome 19p13.3.
Thyrotoxic (hypokalemic) periodic paralysis (TPP) is a frequent complication of thyrotoxicosis among Chinese men. To determine the genetic association of TPP, we studied 97 male TPP patients, 77 Graves' disease patients without TPP, and 100 normal male subjects. Mutations of the voltage-dependent calcium channel (Ca(v)1.1), sodium channel (Na(v)1.4), and potassium channel (K(v)3.4), and association of the microsatellite markers on chromosome 1 in the region of the Na/K-ATPase subunits alpha1, alpha2, and beta1 were studied. None of the TPP patients carried the known mutations in Ca(v)1.1, Na(v)1.4, and K(v)3.4 genes. There was no association of TPP with the microsatellite markers that mapped to 1p13, 1q21-23, and 1q22-25. We detected 12 single nucleotide polymorphisms (SNPs) in Ca(v)1.1 in our population, of which three were novel. Significant differences in the SNP genotype distribution between TPP compared with Graves' disease controls and normal controls were seen at the 5' flanking region nucleotide (nt) -476 (P = 0.02), intron 2 nt 57 (P < 0.01), and intron 26 nt 67 (P < 0.001). Because these SNPs lie at or near the thyroid hormone responsive element, it is possible that they may affect the binding affinity of the thyroid hormone responsive element and modulate the stimulation of thyroid hormone on the Ca(v)1.1 gene.
Childhood absence epilepsy (CAE), a common form of idiopathic generalized epilepsy, accounts for 5%-15% of childhood epilepsies. To map the chromosomal locus of persisting CAE, we studied the clinical and electroencephalographic traits of 78 members of a five-generation family from Bombay, India. The model-free affected-pedigree member method was used during initial screening with chromosome 6p, 8q, and 1p microsatellites, and only individuals with absence seizures and/or electroencephalogram 3-4-Hz spike- and multispike-slow wave complexes were considered to be affected. Significant P values of .00000-.02 for several markers on 8q were obtained. Two-point linkage analysis, assuming autosomal dominant inheritance with 50% penetrance, yielded a maximum LOD score (Zmax) of 3.6 for D8S502. No other locus in the genome achieved a significant Zmax. For five smaller multiplex families, summed Zmax was 2.4 for D8S537 and 1.7 for D8S1761. Haplotypes composed of the same 8q24 microsatellites segregated with affected members of the large family from India and with all five smaller families. Recombinations positioned the CAE gene in a 3.2-cM interval.
Worldwide, the incidence of motor neuron disease (MND) has been increasing steadily over recent decades. We reported a follow-up epidemiology study of MND in this locality. We identified the subjects from the computer database of the government hospital system between 1 January 1997 and 31 January 2002 by searching the ICD code starting from 335.xx. Every retrieved case or their records were reviewed and validated by neurologist(s) of the responsible regional hospitals which the patients attended. One hundred and twenty cases from seven regional hospitals (serving 48.05% of the HKSAR population) were identified, validated and confirmed to be MND or related diseases. Ninety-eight new cases were diagnosed during the study period. Average age of onset was 58.76 years; SD 14.12 (28-89) years. Male to female ratio was 1.72:1. Peak age of onset was 60-64 years without sex difference. The adjusted incidence rate was 0.60/100,000/year. The adjusted point prevalence at the prevalence date (31 January 2001) was 3.04/100,000. Despite the incidence and prevalence of MND among Hong Kong Chinese, it remained low compared to worldwide figures, and our data suggested a significant rise of MND or related disease in the last decade. A territory-wide prospective epidemiological study is indicated.
Purpose:To determine whether diffusion abnormalities can be observed in nonsymptomatic family members with a known causative Cu/Zn superoxide dismutase mutation (asymptomatic familial amyotrophic lateral sclerosis; AFALS ϩSOD1 ) in a family with autosomal dominant familial amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI).
Materials and Methods:A total of eight AFALS ϩSOD1 subjects (aged 17-43 years) were age-matched with 13 healthy controls (aged 19 -45 years) without SOD1 mutations. DTI was carried out on a 1.5T scanner. The diffusion index maps derived were then normalized spatially for voxelbased analysis. region of interest (ROI)-based analysis was also carried out.Results: Our voxel-based and ROI-based analysis showed that AFALS ϩSOD1 subjects have decreased fractional anisotropy (FA) (0.5401 vs. 0.5168, P Ͻ 0.05) and increased tensor trace (TT) (2.5854 ϫ 10 -3 mm 2 /second vs. 2.6226 ϫ 10 -3 mm 2 /second, P Ͻ 0.04) at the posterior limb of the internal capsule compared to the control subjects. Increased radial diffusivity (E (2,3)/2 ) was detected on both sides (right ϭ 0.5710 ϫ 10 -3 mm 2 /second vs. 0.5943 ϫ 10 -3 mm 2 /second, P Ͻ 0.05; left ϭ 0.5666 ϫ 10 -3 mm 2 / second vs. 0.5872 ϫ 10 -3 mm 2 /second, P Ͻ 0.05). No significant change in axial diffusivity (E 1 ) was detected.
Conclusion:Abnormal diffusivity was found at the posterior limb of the internal capsule in AFALS ϩSOD1 subjects, hitherto unreported. Our results suggest that DTI may detect diffusion abnormalities in AFALS ϩSOD1 subjects before symptoms develop.
The prevalence of epilepsy in HKSAR is more common than previously thought. The data retrieved is useful for planning and allocation of health resources for patients with seizure disorders.
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