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Segregation of Allgrove (triple-A) syndrome in Puerto Rican kindreds with chromosome 12 (12q13) polymorphic markers
Ist Teil von
Proceedings of the Association of American Physicians, 1997-09, Vol.109 (5), p.478-482
Ort / Verlag
United States
Erscheinungsjahr
1997
Quelle
MEDLINE
Beschreibungen/Notizen
Allgrove syndrome (AS), also known as triple-A syndrome, is a rare cause of congenital adrenal insufficiency due to adrenocorticotropic hormone resistance. It is inherited in an autosomal recessive manner and is associated with achalasia, alacrima, and other neurological abnormalities, including autonomic, sensory, and upper- and lower-motor neuropathy, deafness, and mental retardation. Although the etiology of AS remains unknown, recently the disease was linked to a chromosome 12 locus (corresponding cytogenetic band 12q13) in consanguineous families of European ancestry. In the present study, we investigated four nonconsanguineous families with documented inheritance of AS for linkage with the reported 12q13 locus. Eighteen subjects were studied, of whom five were affected by AS. DNA was extracted from peripheral blood lymphocytes and amplified by standard methods with primers from polymorphic sequence tagged sites (STSs) located in the chromosome 12q13 region. Two-point logarithm-of-odds (LOD) score analysis revealed a maximum LOD score of 1.7 for STSs D12S361 and D12S368 without any recombinants [recombination distance (theta) = 0]. Multipoint linkage analysis defined an area of estimated genetic distance less than 0.5 cM (approximately 500,000 bp) between STSs D12S361 and D12S359 that is most likely to contain the AS gene(s). We conclude that, in Puerto Rican families, AS segregates with polymorphic markers that have been mapped to the chromosome 12q13 locus, revealing the absence of heterogeneity for this syndrome in a genetically distinct population. Candidate genes in the region include those that code for several of the keratin proteins, transcription factors, and others.