High prevalence of a point mutation in the porphobilinogen deaminase gene in Dutch patients with acute intermittent porphyria

Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized by a deficiency of porphobilinogen deaminase (PBGD). Up to now 14 different mutations have been described. In an effort to investigate the molecular epidemiology of AIP we have undertaken a systematic study of different exons of the PBGD gene from a large number of unrelated patients. Here, exon 8 from 82 unrelated Dutch and French AIP patients was examined using single strand confirmation polymorphism analysis (SSCP) after polymerase chain reaction (PCR) amplification. A single base mutation, C to T, at position 346 of the sequence coding for PBGD was observed in 15 Dutch families but in only 1 French family. A simple PCR assay is described to facilitate the diagnosis of this common mutation at the DNA level.     

Paternal duplication of chromosome 5q11.2–5q14 in a male born with craniostenosis,ear tags,kidney dysplasia and several other anomalies

A de novo duplication of the proximal part of the long arms of chromosome 5 was found in a male born with craniostenosis, ear tags and kidney dysplasia. The nature of the chromosomal aberration was defined by fluorescence in situ hybridization and the orgin of the duplication was traced by polymorphic DNA markers. A comparison is made with the published cases showing similar duplications in the long arm of chromosome 5.     

Genetic mapping of the erythropoietin receptor gene

We describe a novel, highly informative (polymorphism information content, PIC, = 0.86) simple sequence repeat polymorphism at the 5 end of the gene encoding the human erythropoietin receptor (EPOR) previously assigned to 19pl3.2 by in situ hybridization. Fourteen different allelic size variants were identified in 12 families of the CEPH (Centre d'Etude du Polymorphisme Humain) family panel of 40 families. In pairwise linkage 16 of the 65 chromosome 19 markers reported to the CEPH database gave a lod score exceeding 3.0 when tested against EPOR. The most likely location of EPOR within a framework of 10 markers including orientation and information on reported physical assignments was pter-[INSR-D1 9S177-D19S176]-D 19S24-LDLR-EPOR-cen-D-19S7-D19S49-D19S75-D19S47-APOC2-qter, placing EPOR as the most proximal of the tested loci on the short arm. On an 11-point map the position and order for all other loci except INSR were supported by the data with odds exceeding 1,000:1. The polymorphism at the 5 end of EPOR should provide a useful landmark marker for future mapping studies of this region.     

X-linked myoclonus epilepsy explained as a maternally inherited mitochondrial disorder

A family with myoclonus epilepsy has been described previously as suffering from an X-linked disorder, because at least four males were affected, and only mild and variable symptoms were seen in some female carriers. In this family, we have now identified a mitochondrial AG (8344) heteroplasmic point mutation. This point mutation has been described in families with maternally inherited myoclonus epilepsy and ragged red fibers. The degree of severity of the disorder in the different family members was reflected in the relative quantity of mutated mitochondrial DNA. It is concluded that the mode of inheritance in this family is not X-linked but maternal.     

Life history traits of Mediterranean brown trout (Salmo trutta complex) in Pyrenean headwater streams

Ichthyological Research - The Mediterranean brown trout (Salmo trutta complex) is native to basins draining to the Western Mediterranean Sea, and natural populations are currently declining in...