European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Genetic analysis, linkage, and association
G. Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France.
Paragangliomas and phaeochromocytomas are neuroendocrine tumors
derived from parasympathetic and sympathetic nervous systems.
Three genes have been associated with non syndromic paragangliomas:
SDHB, SDHC and SDHD.
We studied the coding sequence of these genes by dHPLC (denaturing
High Performance Liquid Chromatography) followed by sequencing
of the shifted bands. We developed MP/LC (Multiplex PCR Liquid
Chromatography) for the detection of large genomic rearrangements.
We analyzed 21 positive control cases and detected 100% of variants:
20 variants by dHPLC and one deletion of the exon 1 of SDHB
by MP/LC.
We studied 123 unrelated index cases presenting paraganglioma and/
or phaeochromocytoma for which syndromic possibilities were excluded
(negative sequencing of the genes RET and VHL). The sequencing
of abnormal profiles in dHPLC allowed identification of 38 different
variants (including 11 unpublished in literature): 17 polymorphisms, 3
variants with unknown pathogenic caracteristics and 18 pathogenic
mutations: 8 in SDHB, 4 in SDHC and 6 in SDHD (7 missense, 3 nonsense,
7 frameshift and 1 splice site mutation). For 14 remaining negative
patients we looked for large genomic rearrangements by MP/LC
but none variant of this type was highlighted.
Genetic analysis with dHPLC and MP/LC allows us to systematically
analyze SDHB, SDHC and SDHD for small mutations or large rearrangement
in all our patients. We discuss genotype-phenotype correlations
about our patients.
We use complementary genetic technics to complete clinical studies
of a patient and his family. This approach can be extended to whole
genetic pathologies tested in diagnosis.
P1061. Parkin analysis in early onset Parkinson Disease
F. Sironi 1,2 , P. Primignani 1 , M. Zini 2 , S. Ricca 2,1 , T. Brambilla 1,2 , C. Ruffmann 2 , S.
Tunesi 3 , A. Antonini 2 , A. Zecchinelli 2 , C. Mariani 2 , D. A. Coviello 1 , M. Travi 1 , G.
Pezzoli 2 , S. Goldwurm 2 ;
1 Fondazione IRCCS Opedale Maggiore Policlinico, Mangiagalli e Regina Elena,
Milan, Italy, 2 Istituti Clinici di Perfezionamento, Parkinson Institute, Milan, Italy,
3 Institute of Medical Statistics and Biometry, Univerity of Milan, Milan, Italy.
Parkinson’s disease (PD) is the second most common neurodegenerative
disorder with a prevalence of 2% over 65 years of age. A strong
genetic component is present when the disorder begins before 40
years of age. The parkin gene (PARK2 - 6q25.2-27; OMIM: 602544) is
the most common cause associate with autosomal recessive-juvenile
parkinsonism.
146 PD patients (26.7% familial - 73.3% sporadic) with onset