Autosomal dominant Parkinson%26apos;s disease in a large German pedigree

作者：Brueggemann N; Kuelper W; Hagenah J; Bauer P; Pattaro C; Tadic V; Lohnau T; Winkler S; Toennies H; Sprenger A; Pramstaller P; Rolfs A; Siebert R; Riess O; Vieregge P; Lohmann K; Klein C^*

来源：Acta Neurologica Scandinavica, 2012, 126(2): 129-137.

DOI：10.1111/j.1600-0404.2011.01621.x

• genetics
• linkage analysis
• movement disorders
• parkinson%26apos
• s disease

Bruggemann N, Kulper W, Hagenah J, Bauer P, Pattaro C, Tadic V, Lohnau T, Winkler S, Tonnies H, Sprenger A, Pramstaller P, Rolfs A, Siebert R, Riess O, Vieregge P, Lohmann K, Klein C. Autosomal dominant Parkinsons disease in a large German pedigree. ?Acta Neurol Scand: 2012: 126: 129-137. (C) 2011 John Wiley %26 Sons A/S. Objective While several genes have been identified to cause Parkinson%26apos;s disease (PD), monogenic forms explain only a small proportion of cases. We report clinical and genetic results in a large family with late-onset autosomal dominant PD. Methods Thirty-eight family members of a five-generation Northern German PD family underwent a detailed neurologic examination, and transcranial sonography was performed in fifteen of them. Comprehensive mutation analysis of known PD-causing genes and a genome-wide linkage analysis were performed. Results Late-onset definite PD was found in five subjects with a mean age at onset of 63 years. Another six individuals presented either with probable/possible PD or with subtle parkinsonian signs. Six members with a mean age of 79 years had an essential tremor phenotype. Mode of PD inheritance was compatible with autosomal dominant transmission. One of three examined patients with definite PD demonstrated an increased area of substantia nigra hyperechogenicity upon transcranial sonography. Comprehensive linkage and mutational analysis excluded mutations in known PD-causing genes. Genome-wide linkage analysis suggested a putative disease gene in an 11.3-Mb region on chromosome 7p1521.1 with a multipoint LOD score of 2.0. Conclusions The findings in this family further demonstrate genetic heterogeneity in familial autosomal dominant late-onset PD.

• 出版日期2012-8
• 单位河北医科大学