Triple A syndrome - Clinical aspects and molecular genetics

9th Conference on the Adrenal Cortex -- JUN 17-20, 2000 -- UNIV TORONTO, ST MICHAELS COLL, TORONTO, CANADAWOS: 000166064600039PubMed ID: 11196451The triple A syndrome or Allgrove syndrome (MIM*231550) is characterized by adrenocorticotropic hormone (ACTH) resistant Adrenal insufficiency, Achalasia of the cardia and Alacrima. In addition to the main features, patients frequently suffer from neurological disturbances. Dermatological abnormalities such as palmoplantar hyperkeratosis as well as other signs like short stature, microcephaly and osteoporosis point to the multisystemic character of the disorder. The molecular defect of the autosomal recessively inherited triple A syndrome is not known. We initially performed a systematic genome linkage scan in eight triple A families and were able to map the syndrome to a 6 cM interval on human chromosome 12q13 near the type II keratin gene cluster. A refinement of the triple A critical region was achieved by detailed haplotype analysis in a further 37 families from different ethnic backgrounds. There was no indication of genetic heterogeneity. The achalasia-alacrima (AA) syndrome which has been defined as a distinct clinical entity (MIM 200440) is most likely a variant of the triple A syndrome as shown by haplotype analysis in three AA families. We constructed a high-resolution BAC/PAC-based transcript map of the region which will greatly facilitate the identification of the triple A syndrome gene. The considerable intra- and interfamilial variability of the severity of the disorder implies a variable expression of an impaired pleiotropically acting gene.Canadian Life Technologies Inc, Hoffman La Roche Ltd, Marcel Dekker Inc, Nikon, Qiagen Inc, Roche Diagnost, VWR Canla

The United Kingdom Childhood Cancer Study: objectives, materials and methods. UK Childhood Cancer Study Investigators.

An investigation into the possible causes of childhood cancer has been carried out throughout England, Scotland and Wales over the period 1991-1998. All children known to be suffering from one or other type of the disease over periods of 4-5 years have been included, and control children matched for sex, age and area of residence have been selected at random from population registers. Information about both groups of children (with and without cancer) has been obtained from parental questionnaires, general practitioners' and hospital records, and from measurement of the extent of exposure to radon gas, terrestrial gamma radiation, and electric and magnetic fields. Samples of blood have also been obtained from the affected children and their parents and stored. Altogether 3,838 children with cancer, including 1,736 with leukaemia, and 7,629 unaffected children have been studied. Detailed accounts are given of the nature of the information obtained in sections describing the general methodology of the study, the measurement of exposure to ionizing and non-ionizing radiation, the classification of solid tumours and leukaemias, and the biological material available for genetic analysis