Immunoglobulin G4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is a rare condition with symptoms often mimicking malignancy, infection, or other autoimmune diseases. This case report describes the unique case of a 62-year-old male initially diagnosed with IgG4-SC, followed by subsequent diagnosis of cholangiocarcinoma. Biliary tract cancer in the setting of IgG4 related disease has been previously described; however, this patient course is novel as it encompasses the spectrum of challenges in IgG4-SC management, including diagnostic uncertainty, risk of infection with immunosuppressive agents, and development of malignancy diagnosed shortly following IgG4-SC diagnosis. We review the literature of management, outcomes, and malignancy risk and furthermore, highlight a promising recent therapy in treatment of IgG4 related disease, inebilizumab.

No abstract available.
Perforator Flap* ; Thigh*

No abstract available.
Perforator Flap* ; Thigh*

OBJECTIVESTo formulate an equation for fine mapping of disease loci under complex conditions and determine the marker-disease distance in a specific case using this equation.

METHODSLewontin's linkage disequilibrium (LD) measure D' was used to formulate an equation for mapping disease genes in the presence of phenocopies, locus heterogeneity, gene-gene and gene-environment interactions, incomplete penetrance, uncertain liability and threshold, incomplete initial LD, natural selection, recurrent mutation, high disease allele frequency and unknown mode of inheritance. This equation was then used to determine the distance between a marker ( epsilon 4 within the apolipoprotein E gene, APOE) and Alzheimer's disease (AD) loci using published data.

RESULTSAn equation was formulated for mapping disease genes under the above conditions.If these conditions are present but ignored, then recombination fraction theta between marker and disease loci will be either overestimated or estimated with little bias. Therefore, an upper limit of theta can be obtained. AD has been found to be associated with the marker allele epsilon 4 in Africans, Asians, and Caucasians. This suggests that the AD- epsilon 4 allelic LD predates the divergence of peoples occurring 100 000 years ago. With the age of AD- epsilon 4 allelic LD so estimated, the maximal distance was calculated to be 23.2 kb (mean 5.8 kb).

CONCLUSIONS(1) A method is developed for LD mapping of susceptibility genes. (2) A mutation within the APOE gene itself, among others, is responsible for the susceptibility to AD, which is supported by recent evidence from studies using transgenic mice.

Alzheimer Disease ; genetics ; Chromosome Mapping ; Confidence Intervals ; Genetic Predisposition to Disease ; genetics ; Humans ; Linkage Disequilibrium ; Mutation