BACKGROUND AND PURPOSE: Familial aggregation of intracranial aneurysms (IAs) indicates a genetic role in the pathogenesis of this disease. Despite a number of reported susceptibility loci, no disease-causing gene variants have been identified. In this study, we used a parametric genomewide linkage approach to search for new IA susceptibility loci in a large Caucasian family. METHODS: The affection status of family members with clinical signs of IA was confirmed with medical records or through radiological or surgical examinations. All other relatives were screened using MR angiography. Genomewide linkage analysis was performed on 35 subjects using approximately 250 000 single nucleotide polymorphic markers. RESULTS: Ten individuals had an IA. Linkage analysis using a dominant model showed significant linkage to a 7-cM region in 13q14.12-21.1 with a maximum logarithm of odds score of 4.56. CONCLUSIONS: A new IA susceptibility locus on 13q was identified, adding to the number of IA loci already reported. Given that no coding variants have been reported to date, it is possible that alternative genetic variants such as regulatory elements or copy number variation are important in IA pathogenesis. We are proceeding with attempts to identify such variants in our locus.
BACKGROUND AND PURPOSE:Familial aggregation of intracranial aneurysms (IAs) indicates a genetic role in the pathogenesis of this disease. Despite a number of reported susceptibility loci, no disease-causing gene variants have been identified. In this study, we used a parametric genomewide linkage approach to search for new IA susceptibility loci in a large Caucasian family. METHODS: The affection status of family members with clinical signs of IA was confirmed with medical records or through radiological or surgical examinations. All other relatives were screened using MR angiography. Genomewide linkage analysis was performed on 35 subjects using approximately 250 000 single nucleotide polymorphic markers. RESULTS: Ten individuals had an IA. Linkage analysis using a dominant model showed significant linkage to a 7-cM region in 13q14.12-21.1 with a maximum logarithm of odds score of 4.56. CONCLUSIONS: A new IA susceptibility locus on 13q was identified, adding to the number of IA loci already reported. Given that no coding variants have been reported to date, it is possible that alternative genetic variants such as regulatory elements or copy number variation are important in IA pathogenesis. We are proceeding with attempts to identify such variants in our locus.
Authors: Teresa Santiago-Sim; Xiaoqian Fang; Morgan L Hennessy; Stephen V Nalbach; Steven R DePalma; Ming Sum Lee; Steven C Greenway; Barbara McDonough; Georgene W Hergenroeder; Kyla J Patek; Sarah M Colosimo; Krista J Qualmann; John P Hagan; Dianna M Milewicz; Calum A MacRae; Susan M Dymecki; Christine E Seidman; J G Seidman; Dong H Kim Journal: Stroke Date: 2016-11-15 Impact factor: 7.914
Authors: Emília Ilona Gaál; Perttu Salo; Kati Kristiansson; Karola Rehnström; Johannes Kettunen; Antti-Pekka Sarin; Mika Niemelä; Antti Jula; Olli T Raitakari; Terho Lehtimäki; Johan G Eriksson; Elisabeth Widen; Murat Günel; Mitja Kurki; Mikael von und Zu Fraunberg; Juha E Jääskeläinen; Juha Hernesniemi; Marjo-Riitta Järvelin; Anneli Pouta; Christopher Newton-Cheh; Veikko Salomaa; Aarno Palotie; Markus Perola Journal: PLoS Genet Date: 2012-03-15 Impact factor: 5.917
Authors: Mark K Bakker; Suze Cobyte; Frederic A M Hennekam; Gabriel J E Rinkel; Jan H Veldink; Ynte M Ruigrok Journal: Eur J Hum Genet Date: 2022-03-01 Impact factor: 5.351