1/4. Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus using 34 novel microsatellite markers, genomic structure, and exclusion of six known genes in the region.An autosomal recessive nonsyndromic deafness locus, DFNB10, was previously localized to a 12-cM region near the telomere of chromosome 21 (21q22.3). This locus was discovered in a large, consanguineous Palestinian family. We have identified and ordered a total of 50 polymorphic microsatellite markers in 21q22.3, comprising 16 published and 34 new markers, precisely mapped and ordered on BAC/cosmid contigs. Using these microsatellite markers, the locus for DFNB10 has been refined to an area of less than 1 Mb between markers 1016E7.CA60 and 1151C12.GT45. Six previously published cDNAs were mapped to this critical region, and their genomic structures were determined to facilitate mutation analysis in DFNB10. All six genes in this region (in order from centromere to telomere: White/ABCG1, TFF3, TFF2, TFF1, PDE9A, and NDUVF3) have been screened and eliminated as candidates for DFNB10. The new microsatellite markers and single nucleotide polymorphisms identified in this study should enable the refined mapping of other genetic diseases that map to 21q22.3. In addition, the critical region for DFNB10 has been reduced to a size amenable to an intensive positional cloning effort.- - - - - - - - - - ranking = 1keywords = genetic disease (Clic here for more details about this article) |
2/4. familial mediterranean fever in 2 Japanese families.We describe 3 Japanese patients in 2 families with familial mediterranean fever (FMF) as determined by gene analysis. FMF is an ethnically related, genetic disease, occurring commonly in some Mediterranean populations. The FMF gene (MEFV) mutation found in our patients is M694I. The patients may be remote from East Asian extraction.- - - - - - - - - - ranking = 1keywords = genetic disease (Clic here for more details about this article) |
3/4. Chemotherapy in small bowel adenocarcinoma associated with celiac disease: a report of three cases.Tumors of the small intestine are rare and usually occur in association with genetic disease and chronic intestinal inflammation. We report three cases of small bowel adenocarcinoma in patients affected by celiac disease who received a safe chemotherapy regimen (FOLFOX IV or LV5FU2) after tumor resection.- - - - - - - - - - ranking = 1keywords = genetic disease (Clic here for more details about this article) |
4/4. Mechanistic associations of a mild phenotype of immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome.BACKGROUND & AIMS: The syndrome of immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is a rare disorder resulting in the expression of multiple autoimmune and allergic features. Early onset enteropathy and type 1 diabetes (T1D) are the most common clinical features. The IPEX syndrome is caused by mutations of the FOXP3 gene, which is essential for the development of regulatory T cells (Treg). We describe 2 unrelated patients with IPEX syndrome with a mild clinical phenotype and with novel FOXP3 mutations and the phenotypic and functional characterization of their Treg cells. methods: The FOXP3 gene was analyzed by sequencing amplimers from genomic dna. Treg cells were characterized by evaluating the number of CD4 CD25 T cells and their functional ability to suppress the proliferation of autologous CD4 CD25- effector T cells stimulated with anti-CD3 and anti-CD28 antibodies. RESULTS: A 7-year-old boy and a 24-year-old man presented with autoimmune enteropathy characterized by early onset persistent diarrhea not associated with T1D or other endocrinopathies. These 2 patients carry novel FOXP3 mutations that do not abrogate the function of the forkhead domain. They have normal numbers of CD4 CD25 T lymphocytes, however, these show severely defective suppressive function in vitro. CONCLUSIONS: Our 2 patients show that IPEX patients may present with early onset enteropathy and long-term survival without T1D or other endocrinopathies. This milder phenotype may be associated with FOXP3 mutations that do not abrogate the function of the forkhead domain.- - - - - - - - - - ranking = 0.17102300490432keywords = x-linked (Clic here for more details about this article) |