Biomedical subjects

Niklas Dahl

Publications and source records attributed to Niklas Dahl.

23 records · Page 2Linked to original sources

PubMed2002

Gene transfer improves erythroid development in ribosomal protein S19-deficient Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by a specific deficiency in erythroid progenitors. Forty percent of the patients are blood transfusion-dependent. Recent reports show that the ribosomal protein S19 (RPS19) gene is mutated in 25% of all patients with DBA. We constructed oncoretroviral vectors containing the RPS19 gene to develop gene therapy for RPS19-deficient DBA. These vectors were used to introduce the RPS19 gene into CD34(+) bone marrow (BM) cells from 4 patients with DBA with RPS19 gene mutations. Overexpression of the RPS19 transgene increased the number of erythroid colonies by almost 3-fold. High expression levels of the RPS19 transgene improved erythroid colony-forming ability substantially whereas low expression levels had no effect. Overexpression of RPS19 had no detrimental effect on granulocyte-macrophage colony formation. Therefore, these findings suggest that gene therapy for RPS19-deficient patients with DBA using viral vectors that express the RPS19 gene is feasible.

Adult↗

PubMed2002

[Incontinentia pigmenti. A rare disease with many symptoms].

Incontinentia pigmenti, also known as Bloch-Sulzberger syndrome, is a rare multi-systemic disorder. The disease is characterised by abnormalities in ectodermal tissues including the skin, eyes, central nervous system and dentition. It is inherited as an X-linked dominant trait and is usually fatal for male fetuses. Thirty-eight Swedish patients from 16 families were identified. Thirty patients were examined clinically and their DNA were analysed for deletions in the NEMO-gene. The disease showed a large clinical variability even within families and the common deletion in the NEMO-gene was found present in 70% of the families.

Brain Diseases↗

PubMed2002

Familial transient erythroblastopenia of childhood is associated with the chromosome 19q13.2 region but not caused by mutations in coding sequences of the ribosomal protein S19 (RPS19) gene.

Transient erythroblastopenia of childhood (TEC) is a rare condition, which at onset may be difficult to distinguish from Diamond-Blackfan anaemia (DBA). We have previously shown that mutations in the ribosomal protein S19 gene (RPS19) cause DBA. In order to clarify whether TEC and DBA are allelic, we investigated the segregation of markers spanning the RPS19 gene region on chromosome 19q13.2 and performed sequence analysis of all exons in the RPS19 gene in seven TEC sibling pairs. Linkage analysis supported allelism for TEC and DBA at the RPS19 gene locus and implies molecular mechanisms other than structural mutations in the RPS19 gene.

Adult↗

PubMed2002

Marrow failure.

This chapter describes the clinical presentation and molecular basis of two inherited bone marrow failure syndromes, Fanconi anemia (FA), and Diamond-Blackfan anemia (DBA). It also provides an update on diagnostic and therapeutic approaches to bone marrow failure of all types (inherited and acquired) in pediatric patients. In Section I, Dr. Alan D'Andrea reviews the wide range of clinical manifestations of Fanconi anemia. Significant advances have been made in understanding the molecular pathogenesis of FA. On the basis of these advances, new diagnostic assays and treatment options are now available. In Section II, Dr. Niklas Dahl examines the clinical features and molecular pathogenesis of Diamond-Blackfan anemia. The possible links between the RPS19 gene (DBA gene) and the erythropoiesis defect are considered. In Section III, Drs. Eva Guinan and Akiko Shimamura provide an algorithm for the diagnostic evaluation and treatment of children with inherited or acquired aplastic anemia. Through the presentation of a case study of a pediatric patient with bone marrow failure, he provides an overview of the newest tests and treatment options.

Adult↗

PubMed2002

The aquaporin-2 water channel in autosomal dominant primary nocturnal enuresis.

PURPOSE: Nocturnal enuresis is one of the most common diagnoses in a pediatric clinic. Recently, linkage analysis revealed a 2-point lod score of 4.2 in 6 families with dominant primary nocturnal enuresis around the aquaporin-2 (AQP2) water channel locus. Since primary nocturnal enuresis is ameliorated by desmopressin, AQP2 expression is increased by desmopressin and AQP2 is essential for concentrating urine, we determined whether a mutation in the AQP2 gene could cause primary nocturnal enuresis in these families. MATERIALS AND METHODS: Genomic DNAs of several patients from the 6 families were analyzed for disease causing mutations in the 4 exons of the AQP2 genes. RESULTS: In 1 family a G to A transition in the intron 1 splice donor site was found but it was also found in healthy subjects. In another family a C to T transition in the intron 1 splice acceptor region was identified but it was often found in splice acceptor sites. In 2 families a C to T transition was identified in the coding region of exon 3 but this mutation did not lead to a changed amino acid. CONCLUSIONS: Since no mutation in the AQP2 coding sequence was found, while this is essential for involvement in dominant primary nocturnal enuresis, the AQP2 gene is excluded as a candidate for autosomal dominant PNE in these families in which the disease co-segregates with chromosome 12q.

Aquaporin 2↗