By using all the genetic linkage data available between Von Recklinghausen neurofibromatosis (VRNF) and various loci on the autosomes, a graphical display of all the non-excluded areas is presented The probability of VRNF being on any of the 22 autosomes is also shown The exclusion map presented is for 90 markers that have been localised relatively accurately Data are also presented for a further 24 markers that have not yet been adequately localised This exclusion map shows that most of the genome has been excluded as a likely location of any locus responsible for this disorder in the majority of families Chromosomes 5, 10, 17, and 18 remain largely unexcluded Concentration on these parts of the genome should help in the identification of the site of the VRNF gene

https://jmg.bmj.com/content/jmedgenet/24/9/515.full.pdf

An exclusion map for Von Recklinghausen neurofibromatosis.

The von Recklinghausen neurofibromatosis (NF1) gene has been mapped to the pericentromeric region of chromosome 17. We conducted linkage analyses of NF1 by using 10 polymorphic DNA markers from this chromosomal region. We ascertained 20 American Caucasian NF1 families (163 individuals, 98 NF1 affected) in Michigan and Ohio and also studied a large family ascertained primarily in North Carolina. The following markers were used in this study: HHH202, TH17.19, D17Z1, ERBA1, EW203, EW206, EW207, EW301, CRI-L581, and CRI-L946. NF1 did not recombine with either TH17.19 or HHH202 in any of the informative meioses surveyed (maximum lod scores of 17.04 and 7.21, respectively, at a recombination fraction of .00), indicating that these markers map very close to the NF1 gene. We also report evidence of three instances of recombination between NF1 and the centromeric marker D17Z1 (maximum lod score of 13.43 at a recombination fraction of .04), as well as two crossovers between pairs of marker loci. We find no evidence of locus heterogeneity, and our results support the localization of the NF1 gene to proximal chromosome 17q.

A refined genetic map of the region of chromosome 17 surrounding the von Recklinghausen neurofibromatosis (NF1) gene.

Linkage analysis of von Recklinghausen neurofibromatosis to DNA markers on chromosome 17

In 1882, Friedrich von Recklinghausen described a clinical syndrome characterized primarily by tumors arising from nerves, called neurofibromas (Crump, 1981; Warkany, 1981). This report is generally recognized as the most thorough paper describing what is now termed von Recklinghausen neurofibromatosis, or neurofibromatosis type one (NF1). However, a number of previous reports in the medical and other literature as well as ancient artworks are also suggestive of NF1, indicating that this disease has likely been present throughout history (Riccardi and Eichner, 1986). NF1 obtained its misleading nickname of “The Elephant Man Disease” from Sir Frederick Treves’ depiction of Joseph Merrick, an Englishman afflicted with a disfiguring disease with features similar to NF1 (Treves, 1923; Rubenstein et al.,Nucleic Acids Res., 1981; Mulvihill, 1990a). NF1 gained much publicity and notoriety because of Merrick, as a widely performed play was written about his life and both the play and the movie based on it remain popular. However, it is now generally accepted that Merrick probably instead had Proteus syndrome, and the association of NF1 with the Elephant Man is being discouraged (Cohen, 1988), although Merrick’s diagnosis cannot be made with certainty (Hotamisligil, 1989).

Molecular genetics of von Recklinghausen neurofibromatosis.

Linkage relationships of the gene for peripheral neurofibromatosis (NF) were assessed in a large American Caucasian pedigree using two DNA markers located on chromosome 8. Linkage to the thyroglobulin locus, located at 8q24, was excluded (lod less than or equal to -2.0) to 21 cM. Data obtained for the tissue plasminogen activator locus, located at 8p12, excluded linkage to 4 cM. These results exclude between 20 to 30% of chromosome 8 as a possible map location for the NF gene in this family. Comparison of the two DNA markers excluded their linkage to 0.5 cM.

https://jmg.bmj.com/content/jmedgenet/24/9/532.full.pdf

A D Roses

Papers

Linkage analysis of peripheral neurofibromatosis to DNA markers on chromosome 8.