Biomedical subjects

Peter Heutink

Publications and source records attributed to Peter Heutink.

56 records · Page 4Linked to original sources

PubMed2002

A genome-wide search for linkage-disequilibrium with type 1 diabetes in a recent genetically isolated population from the Netherlands.

Type 1 diabetes has a substantial genetic component, with consistent evidence for a susceptibility locus in the HLA-DR/DQ region (chromosome 6p) and the insulin gene region (chromosome 11p). Genome scans have identified >18 other genomic regions that may harbor putative type 1 diabetes genes. However, evidence for most regions varies in different data sets. Given the genetic heterogeneity of type 1 diabetes, studies in homogeneous genetically isolated populations may be more successful in mapping susceptibility loci than in complex outbred populations. We describe a genome-wide search in a recently Dutch isolated population. We identified 43 patients that could be traced back to a common ancestor within 15 generations and performed a genome-wide scan using a combined linkage- and association-based approach. In addition to the HLA locus, evidence for type 1 diabetes loci was observed on chromosome 8q24 (marker D8S1128) and on chromosome 17q24 (marker D17S2059). Both the 8q and 17q localization are supported by allele-sharing at adjacent markers in affected individuals. Statistical evidence for a conserved ancestral haplotype was found for chromosome 8q24.

Alleles↗

PubMedDate not supplied

Dominant hemochromatosis due to N144H mutation of SLC11A3: clinical and biological characteristics.

Hereditary hemochromatosis is classically inherited as a recessive trait but is genetically heterogeneous. Mutations in the HFE and the TFR2 genes account for about 80% of patients and a third locus on chromosome 1q is responsible for juvenile hemochromatosis. We describe here the clinical and biological characteristics of autosomal dominant form of iron overload due to the N144H mutation of the SLC11A3 gene. Clinical signs of iron overload in patients include joint pains, cardiomyopathies, liver fibrosis and hormonal disorders including diabetes mellitus. The main and most common clinical symptoms in this family were joint complaints and early signs of arthrosis. Serum ferritin levels in iron overloaded subjects varied from 31 to 2179 ng/ml and the transferrin saturation from 13 to 88.6%. The iron overload is moderate compared to patients with type 1 hemochromatosis but the deferoxamine test was normal in all patients. The disease in this family segregated as a dominant trait. None of the patients was homozygous or compound heterozygous for any known mutation in the HFE or TFR2 genes. The disease in this family represents a non-classical form of iron overload caused by the N144H mutation in the SLC11A3 gene. The reports of other distinct mutations in SLC11A3 suggest that this gene may be of interest for further etiologic research.

Adult↗