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Background Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs), which due to paradoxical embolization may cause cerebral abscess. Objective To estimate the risk of cerebral abscess among patients with HHT. Methods All patients with HHT included in the Danish HHT data base, between January 1995 and October 2012, have been clinically evaluated for the presence of neurological symptoms and history of previous cerebral abscess. Results A total of 337 patients with HHT have been included in the Danish database. Of these, 264 were screened for the presence of PAVM. In 117 patients, a PAVM was diagnosed; among these, we identified nine patients with a history of cerebral abscess. The prevalence of cerebral abscess among patients with HHT and PAVM was therefore 7.8%. The patients with a history of cerebral abscess were genetically evaluated, and seven had ENG mutations, one had an ALK1 mutation, and in one case, a mutation could not be identified. Conclusion Patients with untreated PAVM have a considerable risk of sustaining cerebral abscesses. A cerebral abscess may be the first symptom leading to an HHT diagnosis. Patients with unexplained cerebral abscess should be evaluated for HHT and PAVM.

Haplotype analysis in 18 apparently unrelated families with familial hypercholesterolaemia (FH) in Iceland has identified at least five different chromosomes cosegregating with hypercholesterolaemia. The most common haplotype was identified in 11 of the 18 families, indicating a responsible for FH in the Icelandic population. By using single-strand conformation polymorphism (SSCP) and direct sequencing of amplified DNA, we identified a novel mutation (a T to a C) in the second nucleotide in the 5' part of intron 4 in the LDL receptor gene. This mutation was present in approximately 60% of the FH families (10/18), supporting the prediction of a common founder. These families could be traced to a common ancestor in half of the cases by going back no further than the eighteenth century. The mutation was predicted to affect correct splicing of exon 4, and analysis at the cellular level demonstrated an abnormal mRNA containing intron 4 sequence in lymphoblastoid cells from a patient carrying this mutation. Translation of the mRNA would lead to a premature stop codon and a truncated nonfunctional protein of 285 amino acids. The novel sequence change created a new restriction site for the restriction endonuclease NlaIII, and using this assay, 29 unrelated individuals with possible FH attending a lipid clinic for treatment were examined for this mutation. Two individuals in this group of patients were found to be carriers of this mutation, supporting the suggestion of a founder mutation. Using this assay for the detection of FH in the Icelandic population should identify > 60% of these individuals.

In order to identify mutations in the low density lipoprotein receptor (LDLR) gene in primary hypercholesterolemia, we screened 100 unrelated German individuals with elevated plasma LDL-C (LDL-C > 4,7 mmol/l) for mutations in the 18 exons and their flanking intronic sequences including the promoter region of the LDL-R gene using a combination of polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE) and direct sequencing. In addition we tested all patients for the presence of mutations in codons 3456 - 3553 of the gene encoding apolipoprotein B-100. In 56 individuals we detected 37 different mutations affecting the LDL-R gene, 16 of which, designated C122R, C127Y, C163W, F179L, R236W, E296X, R553C, V618D, T721I, V785D, G1358+2A, 257delTCTGGAGGT, 657delC, 676insACGGTATGGACTGCAdelGACG, C1205delTCT, 2420delTCCTTCT, have not yet been reported. One proband was a compound heterozygote showing two separate sequence variations (E207X and T705I). Seven patients were heterozygous for the mutation R3500Q within the apoB-100 gene. These results demonstrate that there is a broad spectrum of mutations in the LDL-R gene and that the R3500Q mutation is a frequent cause of hypercholesterolemia in the German population.