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Gene localization for an autosomal dominant familial periodic fever to 12p13
1Department of Cytogenetics and Molecular Genetics, Center for Medical Genetics, Women's and Children's Hospital, North Adelaide, SA 5006, Australia. mulleyj@mail.wch.sa.gov.au
Abstract:
We report gene localization in a family with a benign autosomal dominant familial periodic fever (FPF) syndrome characterized by recurrent fever associated with abdominal pain. The clinical features are similar to the disorder previously described as familial Hibernian fever, and they differ from familial Mediterranean fever (FMF) in that FPF episodes usually do not respond to colchicine and FPF is not associated with amyloidosis. Frequent recombination with the marker D16S2622, <1 Mb from FMF, at 16p13.3, excluded allelism between these clinically similar conditions. Subsequently, a semiautomated genome search detected linkage of FMF to a cluster of markers at 12p13, with a multipoint LOD score of 6.14 at D12S356. If penetrance of 90% is assumed, the FPF gene maps to a 19-cM interval between D12S314 and D12S364; however, if complete penetrance is assumed, then FPF maps to a 9-cM region between D12S314 and D12S1695. This interval includes the dentatorubropallidoluysian atrophy locus, which, with FPF, gave a maximum two-point LOD score of 3.7 at a recombination fraction of 0. This is the first of the periodic-fever genes, other than FMF, to be mapped. Positional candidate genes may now be selected for mutation analysis to determine the molecular basis for FPF. Together with the recent identification of the defective gene in FMF, identification of a gene for FPF might provide new insights into the regulation of inflammatory responses.
Insights
Researchers localized the gene for familial periodic fever (FPF), a recurrent fever syndrome. This finding, distinct from familial Mediterranean fever (FMF), advances understanding of inflammatory response regulation.
Area of Science:
- Genetics
- Immunology
- Human Disease
Background:
- Familial periodic fever (FPF) is an autosomal dominant syndrome with recurrent fevers and abdominal pain.
- FPF shares clinical similarities with familial Hibernian fever but differs from familial Mediterranean fever (FMF) in colchicine response and lack of amyloidosis.
Purpose of the Study:
- To localize the gene responsible for familial periodic fever (FPF).
- To differentiate FPF from other periodic fever syndromes through genetic mapping.
Main Methods:
- Genome search using semiautomated methods.
- Linkage analysis with genetic markers.
- Exclusion of allelism with FMF using marker D16S2622.
- Multipoint LOD score calculation to determine gene linkage at 12p13.
Main Results:
- Linkage of FPF to markers at 12p13 was detected with a multipoint LOD score of 6.14.
- The FPF gene was mapped to a 9-19 cM interval on chromosome 12p13, depending on penetrance assumptions.
- Exclusion of allelism with FMF confirmed FPF as a distinct genetic disorder.
Conclusions:
- The gene for FPF has been successfully mapped, representing a significant step in understanding periodic fever syndromes.
- This localization facilitates the selection of positional candidate genes for mutation analysis.
- Identifying the FPF gene may offer new insights into the regulation of inflammatory responses, complementing FMF research.