ABSTRACT
Asperger disorder (ASP) is one of the autism spectrum disorders (ASD) and is differentiated from autism largely on the absence of clinically significant cognitive and language delays. Analysis of a homogenous subset of families with ASP may help to address the corresponding effect of genetic heterogeneity on identifying ASD genetic risk factors. To examine the hypothesis that common variation is important in ASD, we performed a genome-wide association study (GWAS) in 124 ASP families in a discovery data set and 110 ASP families in a validation data set. We prioritized the top 100 association results from both cohorts by employing a ranking strategy. Novel regions on 5q21.1 (P = 9.7 × 10(-7) ) and 15q22.1-q22.2 (P = 7.3 × 10(-6) ) were our most significant findings in the combined data set. Three chromosomal regions showing association, 3p14.2 (P = 3.6 × 10(-6) ), 3q25-26 (P = 6.0 × 10(-5) ) and 3p23 (P = 3.3 × 10(-4) ) overlapped linkage regions reported in Finnish ASP families, and eight association regions overlapped ASD linkage areas. Our findings suggest that ASP shares both ASD-related genetic risk factors, as well as has genetic risk factors unique to the ASP phenotype.
Subject(s)
Asperger Syndrome/genetics , Polymorphism, Single Nucleotide/genetics , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Genetic Linkage/genetics , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study/methods , Humans , Male , Risk Factors , Young AdultABSTRACT
Autism is a common neurodevelopmental disorder with a significant genetic component and locus heterogeneity. To date, 12 microsatellite genome screens have been performed using various data sets of sib-pair families (parents and affected children) resulting in numerous regions of potential linkage across the genome. However, no universal region or consistent candidate gene from these regions has emerged. The use of large, extended pedigrees is a recognized powerful approach to identify significant linkage results, as these families potentially contain more potential linkage information than sib-pair families. A genome-wide linkage analysis was performed on 26 extended autism families (65 affected, 184 total individuals). Each family had two to four affected individuals comprised of either avuncular or cousin pairs. For analysis, we used a high-density single-nucleotide polymorphism genotyping assay, the Affymetrix GeneChip Human Mapping 10K array. Two-point analysis gave peak heterogeneity limit of detection (HLOD) of 2.82 at rs2877739 on chromosome 14q. Suggestive linkage evidence (HLOD>2) from a two-point analysis was also found on chromosomes 1q, 2q, 5q, 6p,11q and 12q. Chromosome 12q was the only region showing significant linkage evidence by multipoint analysis with a peak HLOD=3.02 at rs1445442. In addition, this linkage evidence was enhanced significantly in the families with only male affected (multipoint HLOD=4.51), suggesting a significant gender-specific effect in the etiology of autism. Chromosome-wide haplotype analyses on chromosome 12 localized the potential autism gene to a 4 cM region shared among the affected individuals across linked families. This novel linkage peak on chromosome 12q further supports the hypothesis of substantial locus heterogeneity in autism.
Subject(s)
Autistic Disorder/genetics , Chromosomes, Human, Pair 12 , Family Health , Genetic Predisposition to Disease , Chromosome Mapping/methods , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 14 , Female , Genotype , Humans , Lod Score , Male , Oligonucleotide Array Sequence Analysis/methods , Polymorphism, Single Nucleotide , Sex FactorsABSTRACT
We analyzed MRI results from 36 patients referred for testing to assess the degree of advancement of non-traumatic avascular necrosis (AVN) of the femoral head in adults (24 cases) or for diagnosis in difficult cases (12 cases). 32 patients were found to have AVN of the femoral head with various degree of advancement, mostly stages III and IV. In three cases the MRI did not show any pathology within the hip joint, and in one case the MRI picture was consistent with a metastatic lesion. This suggests that the value of the MRI as a sensitive diagnostic tool in the early diagnosis of AVN in adults is underestimated.
ABSTRACT
A case of gigantic liposarcoma of the lower extremity in 42 years old female is presented. The tumor grew extremely fast and reached gigantic size. Over one year follow-up did not reveal any local recurrence or metastases.
Subject(s)
Liposarcoma/therapy , Thigh/surgery , Adult , Brachytherapy , Female , Humans , Liposarcoma/diagnosis , Magnetic Resonance Imaging , Radiotherapy, AdjuvantABSTRACT
Treatment of trochanteric fractures, especially in patients who are advanced in age, presents numerous difficulties; the results of treatment are not always satisfactory. The aim of the study was to analyse the results of conservative treatment of trochanteric fractures in 50 patients (31 females and 19 males, 65-94 years of age), who were not qualified for surgery because of sclerosis, cerebral haemorrhage in the past, labile diabetes, senile dementia, an advanced neoplastic disease, circulatory and respiratory insufficiency, or refusal of agreement to the surgery. An adhesion of fracture was obtained in 43 cases (86%). 28 patients (56%) could move with no difficulties and did not suffer from any pain. 7 patients (14%) died (including 2 cases of neoplasm).
Subject(s)
Femur/injuries , Femur/surgery , Fractures, Bone/surgery , Aged , Aged, 80 and over , Female , Humans , Male , Retrospective Studies , Treatment OutcomeABSTRACT
The method and results of uncommon ultrasound treatment in 82 cases of osteomyelitis are presented. The method was supplemented with intraoperative Th 99m isotope diagnostics as well as fluorescence based diagnosis to identify necrotic bone fragments. Ultrasound energy had advantageous effect on soft tissue healing and osteogenesis.