Background and aim: Known colorectal cancer syndromes, such as familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, have been identified in only a small proportion of cases with a family histo...Background and aim: Known colorectal cancer syndromes, such as familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, have been identified in only a small proportion of cases with a family history of disease. In an attempt to identify loci harbouring novel predisposing genes, we have performed a genome wide linkage analysis in 18 colorectal cancer families recruited from the Department of Clinical Genetics at Karolinska Hospital, Sweden. Methods: Multipoint parametric and non-parametric linkage analyses were performed using two affected status criteria, stringent and less stringent. Parametric analysis was performed under the assumption of locus homogeneity and locus heterogeneity. Results: The initial scan performed using the less stringent affected status criteria revealed regions of interest on chromosome 11 (marker D11S1314: heterogeneity logarithm of odds (HLOD) score 1.96, non-parametric LOD (NPL) score 1.28; and marker D11S908: HLOD score 2.10, NPL score 2.16) and chromosome 14 (marker D14S258: HLOD score 2.61, NPL score 2.88). Using the stringent affected status criteria, a locus on chromosome 22 was suggested in the parametric analysis (marker D22S315: HLOD score 1.26). After fine mapping of the regions on chromosomes 11 and 14, HLOD and NPL scores were reduced but still within the range of suggestive linkage. Haplotype analysis revealed overlapping regions between D11S987 and D11S4207 (proximal region), D11S4120 and D11S4090 (distal region), on chromosome 11, and between D14S1038 and D14S1069 on chromosome 14. Conclusion: Our study provides evidence of genetic heterogeneity among Swedish colorectal cancer families. Three novel regions were suggested to be of interest in a proportion of families analysed. Further studies are needed to confirm this result.展开更多
Background: It remains uncertain whether basilar-type migraine (BM) is a subtype of migraine with typical aura (MTA) or a distinct phenotype or genotype. Objective: To analyze the symptomatology, familial distribution...Background: It remains uncertain whether basilar-type migraine (BM) is a subtype of migraine with typical aura (MTA) or a distinct phenotype or genotype. Objective: To analyze the symptomatology, familial distribution, and genotype of BM. Methods: The authors recruited 105 families comprising 362 patients with MTA or BM (International Classification of Headache Disorders-1 criteria). Among these patients, 38 patients from 29 families had BM. In 12 of the families with BM with an apparently dominant inheritance the authors sequenced all exons of the CACNA1A (chromosome 19) and ATP1A2 (chromosome 1) genes responsible for most cases of the autosomal dominantly inherited familial hemiplegic migraine and performed a linkage analysis of chromosome 1 and 19 with a nonparametric or autosomal dominant parametric model using an affected only analysis. Results: BM occurred in 10%(38/362) of patients with MTA. The basilar-type aura had a median duration of 60 minutes and comprised vertigo 61%, dysarthria 53%, tinnitus 45%, diplopia 45%, bilateral visual symptoms 40%, bilateral paresthesias 24%, decreased level of consciousness 21%, hypacusia 21%, and ataxia 5%. The relative frequency of the individual basilar-type symptoms was not different from patients with hemiplegic migraine from a previous study. The patients with BM were equally distributed among the 105 families with MTA (p = 0.37). The attacks of MTA were identical in families with or without BM. No causative mutations and no linkage was identified. Conclusions: Basilar-type aura seemingly may occur at times in any patient with migraine with typical aura. There is no firm clinical, epidemiologic, or genetic evidence that BM is an independent disease entity different from MTA.展开更多
文摘Background and aim: Known colorectal cancer syndromes, such as familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, have been identified in only a small proportion of cases with a family history of disease. In an attempt to identify loci harbouring novel predisposing genes, we have performed a genome wide linkage analysis in 18 colorectal cancer families recruited from the Department of Clinical Genetics at Karolinska Hospital, Sweden. Methods: Multipoint parametric and non-parametric linkage analyses were performed using two affected status criteria, stringent and less stringent. Parametric analysis was performed under the assumption of locus homogeneity and locus heterogeneity. Results: The initial scan performed using the less stringent affected status criteria revealed regions of interest on chromosome 11 (marker D11S1314: heterogeneity logarithm of odds (HLOD) score 1.96, non-parametric LOD (NPL) score 1.28; and marker D11S908: HLOD score 2.10, NPL score 2.16) and chromosome 14 (marker D14S258: HLOD score 2.61, NPL score 2.88). Using the stringent affected status criteria, a locus on chromosome 22 was suggested in the parametric analysis (marker D22S315: HLOD score 1.26). After fine mapping of the regions on chromosomes 11 and 14, HLOD and NPL scores were reduced but still within the range of suggestive linkage. Haplotype analysis revealed overlapping regions between D11S987 and D11S4207 (proximal region), D11S4120 and D11S4090 (distal region), on chromosome 11, and between D14S1038 and D14S1069 on chromosome 14. Conclusion: Our study provides evidence of genetic heterogeneity among Swedish colorectal cancer families. Three novel regions were suggested to be of interest in a proportion of families analysed. Further studies are needed to confirm this result.
文摘Background: It remains uncertain whether basilar-type migraine (BM) is a subtype of migraine with typical aura (MTA) or a distinct phenotype or genotype. Objective: To analyze the symptomatology, familial distribution, and genotype of BM. Methods: The authors recruited 105 families comprising 362 patients with MTA or BM (International Classification of Headache Disorders-1 criteria). Among these patients, 38 patients from 29 families had BM. In 12 of the families with BM with an apparently dominant inheritance the authors sequenced all exons of the CACNA1A (chromosome 19) and ATP1A2 (chromosome 1) genes responsible for most cases of the autosomal dominantly inherited familial hemiplegic migraine and performed a linkage analysis of chromosome 1 and 19 with a nonparametric or autosomal dominant parametric model using an affected only analysis. Results: BM occurred in 10%(38/362) of patients with MTA. The basilar-type aura had a median duration of 60 minutes and comprised vertigo 61%, dysarthria 53%, tinnitus 45%, diplopia 45%, bilateral visual symptoms 40%, bilateral paresthesias 24%, decreased level of consciousness 21%, hypacusia 21%, and ataxia 5%. The relative frequency of the individual basilar-type symptoms was not different from patients with hemiplegic migraine from a previous study. The patients with BM were equally distributed among the 105 families with MTA (p = 0.37). The attacks of MTA were identical in families with or without BM. No causative mutations and no linkage was identified. Conclusions: Basilar-type aura seemingly may occur at times in any patient with migraine with typical aura. There is no firm clinical, epidemiologic, or genetic evidence that BM is an independent disease entity different from MTA.
