Showing papers by "Michael F. McDermott published in 2000"

An autosomal dominant periodic fever associated with AA amyloidosis in a north Indian family maps to distal chromosome 1q.

Abstract: Objective To investigate genetic susceptibility in the first Indian family identified as having an autosomal dominantly inherited periodic fever syndrome. The inflammatory disease was characterized chiefly by arthralgia, skin rashes, and AA amyloidosis. Methods Markers from known periodic fever susceptibility loci were investigated in 7 affected and 11 healthy members of a north Indian family. These included the TNFRSF1A locus (formerly known as TNFRI), which is involved in autosomal dominant tumor necrosis factor receptor–associated periodic syndrome on chromosome 12p13, the familial Mediterranean fever locus (MEFV) on chromosome 16p13, the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) locus on chromosome 12q24, and the Muckle-Wells syndrome/familial cold urticaria (MWS/FCU) locus on distal chromosome 1q44. Results Linkage to both TNFRSF1A and MEFV was definitively excluded, and DNA sequencing of these genes revealed no mutations. Furthermore, there was no evidence of linkage to the HIDS locus. In contrast, significant logarithm of odds scores for 5 markers from the MWS/FCU region were obtained in this family, and the disease segregated with the same haplotype in all affected members. Conclusion We have identified an inherited inflammatory disease in a north Indian family with clinical features overlapping some of those of MWS and FCU. The susceptibility gene maps to distal chromosome 1q44, a region already implicated in both MWS and FCU. Different mutations in the same (or a closely related) gene may be responsible for an inflammatory disease with a broad phenotype among diverse ethnic populations.

Pancreatitis in fibrocalculous pancreatic diabetes mellitus is not associated with common mutations in the trypsinogen gene

Abstract: Background A distinct type of pancreatitis associated with diabetes, termedfibrocalculous pancreatic diabetes (FCPD), has been reported in tropicaldeveloping countries including Bangladesh. The molecular basis forautosomal dominant hereditary pancreatitis (HP) has recently beenattributed to mutations in exons 2 and 3 of the trypsinogen gene. We haveinvestigated the hypothesis that mutations in the aforementioned exons ofthis gene might also predispose to FCPD.Methods Seventy Bangladeshi and 50 South Indian unrelated FCPDpatients and seven South Indian families with FCPD probands were studied.Pancreatic calcification was confirmed by abdominal X-ray, ultrasound and/or ERCP. Established mutations of exons 2 and 3 of the trypsinogen gene werestudied in these subjects by PCR-RFLP analysis and DNA sequencing.Results The mutations found in hereditary pancreatitis were not observedin this collection of FCPD subjects, and complete DNA sequencing of exons 2and 3 of the fourth cationic trypsinogen gene also excluded any newmutations.Conclusions These results indicate that chronic pancreatitis of FCPD isunlikely to be caused by common mutations in the trypsinogen gene.Copyright # 2000 John Wiley & Sons, Ltd.Keywords fibrocalculous pancreatic diabetes; tropical calcific pancreatitis;pancreatitis; trypsinogen gene; mutation; diabetes

Family association studies of markers on chromosome 2q and Type 1 diabetes in subjects from South India.

Abstract: BACKGROUND: Several Type 1 diabetes susceptibility loci have been located to chromosome 2q12-21. However, results have not always been consistent and this may reflect study design and the population analysed. We have used a family-based design to look for an association between Type 1 diabetes and markers located to 2q12-21. METHODS: Ninety-one South Indian families consisting of subjects with Type 1 diabetes and their parents were genotyped for eight polymorphic markers localised to 2q12-21, which includes the interleukin-1 gene cluster. Radiation hybrid mapping was used to localise the map position of D2S308 and D2S363 on 2q12-21. The extended transmission disequilibrium test was used for statistical analysis. RESULTS: No associations were found between Type 1 diabetes and markers located in and around the interleukin-1 gene cluster or the interleukin-1 Type 1 receptor. In contrast, a suggestive association was found between Type 1 diabetes and two closely-linked markers telomeric of the interleukin-1 gene cluster (D2S308 and D2S363, separated by 3.3 cR) (p=0.004 and p=0.002, respectively). CONCLUSION: This preliminary study suggests that a locus close to D2S308 and D2S363 is involved in the aetiology of Type 1 diabetes in the South Indian population.