title: RNA-based mutation screening in German families with Sjögren-Larsson syndrome.
abstract: Sjögren-Larsson syndrome (SLS) is a rare autosomal recessively inherited disorder characterised by mental retardation, spasticity and ichthyosis. SLS patients have a profound deficiency in fatty aldehyde dehydrogenase (FALDH) activity. The human cDNA of FALDH has been shown to map to the SLS locus on chromosome 17p11.2. Here we describe a method based on reverse transcriptase-polymerase chain reaction (RT-PCR) and protein truncation test to identify mutations in the FALDH gene in nine German SLS families. Using this detection system both disease-causing mutations were found in eight of the nine SLS families examined (17/18 chromosomes). Seven different mutations were identified: an exon 2 skipping due to exon 2 splice donor mutation; two different exon 3 splice donor mutations resulting in combined exon 2 and 3 skipping; a 906delT deletion in exon 6; a genomic deletion of about 6 kb including exon 9; a 1277T > G transversion resulting in a Leu426Ter nonsense mutation; and a 1297delGA deletion. Two of the mutations identified, the genomic exon 9 deletion and the 906delT in exon 6 affected five out of seven SLS patients from a small region of Northern Bavaria. Therefore these two mutations accounted for 71% (10/14 chromosomes) of Bavarian SLS alleles and so far have not been described in SLS families from other countries. Our findings do not support our 'historical' hypothesis, that a possible region clustering in Northern Bavaria could be due to the presence of Swedish soldiers during the 30 Years War (1618-1648), but suggest that two mutations causing SLS syndrome originated in Northern Bavaria.
authors.affiliation: Institut für Humangenetik, Universität Erlangen-Nürnberg, Erlangen, Germany. cokraus@humgenet.uni-erlangen.de
authors.forename: C
authors.initials: C
authors.lastname: Kraus
authors.forename: C
authors.initials: C
authors.lastname: Braun-Quentin
authors.forename: W G
authors.initials: WG
authors.lastname: Ballhausen
authors.forename: R A
authors.initials: RA
authors.lastname: Pfeiffer
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D001483:Base Sequence; D018388:Codon, Terminator; D005091:Exons; D005192:Family Health; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation; D005858:Germany; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D016111:Sjogren-Larsson Syndrome / Q000235:genetics*
chemical_list: D018388:Codon, Terminator; D012313:RNA; D000445:Aldehyde Oxidoreductases; C038828:long-chain-aldehyde dehydrogenase