caa a22 4500 397573359 CHVBK 20180308164847.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/hmg/5.12.2061 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.12.2061 Linkage of the Gene for the Triple A Syndrome to Chromosome 12q13 Near the Type II Keratin Gene Cluster [Elektronische Daten] [Angela Weber, Thomas F. Wienker, Martin Jung, Douglas Easton, Heather J. Dean, Claudine Heinrichs, Andre Reis, Adrian J. L. Clark] The triple A or Allgrove's syndrome (MIM*231550) is an autosomal recessive disease characterized by the triad of adrenocorticotropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrima. Since its first description by Allgrove et al. (1978) more than 70 cases from all over the world have been reported. The syndrome manifests itself during the first decade of life with severe hypoglycaemic episodes which can cause sudden death. The frequent association with neurological disorders presenting as a mixed pattern of upper and lower motor neuropathy, sensory impairment, autonomic neuropathy and mental retardation may result in a severely disabling disease. As an additional feature some patients have hyperkeratosis of their palms and soles. We have performed a systematic genome linkage scan in eight triple A families of which three were consanguineous [including the large highly inbred kindred described by Moore et al. (1991)]. We obtained conclusive evidence for linkage of the triple A syndrome locus to markers on chromosome 12q13 (D12S368, θmax = 0, Zmax = 10.81) with no indication of genetic heterogeneity. Haplotype and multipoint analyses suggest that the gene is located on a chromosomal segment flanked by the markers D12S1629 and D12S312 which are 6 cM apart. This region harbors the type II keratin gene cluster, and potential candidate genes include SCN8A and HOXC genes. © 1993 Oxford University Press Weber Angela Department of Paediatrics, University Hospital Dresden, 01307 Dresden, Germany aut Wienker Thomas F. Microsatellite Centre, Max Delbrück Center (MDC) for Molecular Medicine, 13122 Berlin-Buch, Germany aut Jung Martin Microsatellite Centre, Max Delbrück Center (MDC) for Molecular Medicine, 13122 Berlin-Buch, Germany aut Easton Douglas Department of Community Medicine, Institute of Public Health, University of Cambridge, Cambridge CB2 2SR, UK aut Dean Heather J. Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba R3A 0Z2, Canada aut Heinrichs Claudine Children's Hospital Queen Fabiola, Free University of Brussels, Brussels, Belgium aut Reis Andre Microsatellite Centre, Max Delbrück Center (MDC) for Molecular Medicine, 13122 Berlin-Buch, Germany aut Clark Adrian J. L. Department of Chemical Endocrinology, St Bartholomew's Hospital, London EC1A 7BE, UK aut Human Molecular Genetics Oxford University Press 5/12(1996-12), 2061-2066 0964-6906 5:12<2061 1996 5 hmg https://doi.org/10.1093/hmg/5.12.2061 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.12.2061 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Weber Angela Department of Paediatrics, University Hospital Dresden, 01307 Dresden, Germany aut NATIONALLICENCE 700 1- Wienker Thomas F. Microsatellite Centre, Max Delbrück Center (MDC) for Molecular Medicine, 13122 Berlin-Buch, Germany aut NATIONALLICENCE 700 1- Jung Martin Microsatellite Centre, Max Delbrück Center (MDC) for Molecular Medicine, 13122 Berlin-Buch, Germany aut NATIONALLICENCE 700 1- Easton Douglas Department of Community Medicine, Institute of Public Health, University of Cambridge, Cambridge CB2 2SR, UK aut NATIONALLICENCE 700 1- Dean Heather J. Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba R3A 0Z2, Canada aut NATIONALLICENCE 700 1- Heinrichs Claudine Children's Hospital Queen Fabiola, Free University of Brussels, Brussels, Belgium aut NATIONALLICENCE 700 1- Reis Andre Microsatellite Centre, Max Delbrück Center (MDC) for Molecular Medicine, 13122 Berlin-Buch, Germany aut NATIONALLICENCE 700 1- Clark Adrian J. L. Department of Chemical Endocrinology, St Bartholomew's Hospital, London EC1A 7BE, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/12(1996-12), 2061-2066 0964-6906 5:12<2061 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford