CLINICAL AND MOLECULAR GENETIC CHARACTERIZATION OF A FINNISH FAMILY WITH BENIGN INFANTILE CONVULSIONS AND PAROXYSMAL DYSKINESIA
Abstract number :
2.191
Submission category :
Year :
2003
Submission ID :
3852
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Anna-Kaisa Anttonen, Elina Liukkonen, Susanna Ranta, Eija Gaily, Anna-Elina Lehesjoki Department of Medical Genetics, University of Helsinki, Helsinki, Finland; Folkhalsan Institute of Genetics, Helsinki, Finland; HUCH-Laboratory Diagnostics, Helsinki Uni
Benign familial infantile convulsions (BFIC) is a clinically and genetically heterogeneous disorder, which is inherited autosomal dominantly. In some families BFIC has been reported to occur together with paroxysmal dyskinesia (PD). We identified and clinically characterized a large Finnish family in which a phenotype resembling the previously described syndrome manifesting as familial infantile convulsions and paroxysmal choreoathetosis (ICCA) segregates in three generations. A candidate locus approach was undertaken to study the molecular genetic basis of the clinical phenotype in the family.
Medical records of the consenting family members were examined to confirm the diagnosis of BFIC and PD. Microsatellite markers were tested to evaluate known candidate loci. Previously reported loci for BFIC, ICCA and paroxysmal non-kinesigenic dyskinesia (PNKD) on chromosomes 2q24 (BFIC), 2q31-36 (PNKD), 16p11-q12 (ICCA and BFIC), and 19q (BFIC) were studied. With the genotypes received haplotypes were constructed and LOD scores were calculated using the GENEHUNTER 2.1 and MLINK programs at the HGMP (Human Genome Mapping Project) WWW Menu (http://www.hgmp.mrc.ac.uk/).
The family studied has eight affected individuals with variable phenotypes including infantile convulsions with favorable outcome and paroxysmal dyskinesia. The infantile convulsions started at the age of few months and subsided within weeks. The onset of PD was before the age of ten years and the PD symptoms had features of both kinesigenic choreoathetosis and non-kinesigenic dyskinesia. Linkage was found to markers on chromosome 16p12.1 - 16p11.2 near the pericentromeric region. A maximum two-point LOD score of 2.43 (at [theta] = 0.000) was obtained at marker D16S3022 using a penetrance of 80% and a phenocopy rate of 2%. The candidate locus is approximately 5 cM and contains more than 120 already known and predicted genes. Markers spanning the three loci on chromosomes 2q and 19q showed no linkage in this family.
The candidate locus on chromosome 16p overlaps with previous regions defined in families with BFIC and PD. This study further narrows the region to approximately 5 cM.