title: X-linked adrenal hypoplasia congenita: a novel DAX1 missense mutation and challenges for clinical diagnosis in Africa.
abstract: Adrenal hypoplasia congenita (AHC) is a rare disease. The X-linked form of AHC is caused by deletions or mutations in DAX1 gene and has a variable clinical presentation. To date, no data on X-linked AHC in central Africa are available. Here, we report a Congolese pedigree with several cases of unexplained deaths of male infants. A careful analysis of the pedigree of this family lead to the recognition of an X-linked inheritance pattern, with subsequent confirmation in a female heterozygous carrier of a DAX1 missense mutation c.1274G>T, (p.Arg425Ile).The diagnosis of this condition remains challenging in a developing country, since the manifestations of AHC overlap with those of the much more frequently occurring infections; darkening of the skin is difficult to evaluate and there is a lack of access to routine endocrinological testing. The diagnosis was eventually made based on the family pedigree, evoking an X-linked inheritance pattern. This illustrates the necessity for medical and clinical genetics to be part of the curriculum of medical school in developing countries.
authors: Center for Human Genetics, University Hospitals Leuven, Katholieke Universiteit Leuven, Herestraat 49, bus 602, 3000 Leuven, Belgium.
authors: Aimé
authors: A
authors: Lumaka
authors: Gerrye
authors: G
authors: Mubungu
authors: Celestin
authors: C
authors: Nsibu
authors: Bruno-Paul
authors: BP
authors: Tady
authors: Tshilobo
authors: T
authors: Lukusa
authors: Koenraad
authors: K
authors: Devriendt
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000235:genetics*; D000309:Adrenal Insufficiency; D000349:Africa; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics*; D015023:Democratic Republic of the Congo; D017809:Fatal Outcome; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D000075262:Hypoadrenocorticism, Familial; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D005819:Genetic Markers; C539965:NR0B1 protein, human