Uniparental disomy for chromosome 6 results in steroid 21-hydroxylase deficiency: evidence of different genetic mechanisms involved in the production of the disease

Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis caused by mutations in the steroid 21-hydroxylase gene (CYP21) in more than 90% of affected patients. The CYP21 gene is located within the HLA complex locus on chromosome 6 (6p21.3). During a molecular...

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Bibliographic Details
Published in:Journal of medical genetics 1998-12, Vol.35 (12), p.1014-1019
Main Authors: López-Gutiérrez, A U, Riba, L, Ordoñez-Sánchez, M L, Ramírez-Jiménez, S, Cerrillo-Hinojosa, M, Tusié-Luna, M T
Format: Article
Language:English
Subjects:
Adrenal Hyperplasia, Congenital - enzymology
Adrenal Hyperplasia, Congenital - genetics
Adrenals. Adrenal axis. Renin-angiotensin system (diseases)
Biological and medical sciences
Child
Child, Preschool
Chromosomes, Human, Pair 6
Endocrinopathies
Female
Haplotypes
Humans
Infant, Newborn
Male
Medical sciences
Mutation
Non tumoral diseases. Target tissue resistance. Benign neoplasms
Pedigree
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Summary:Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis caused by mutations in the steroid 21-hydroxylase gene (CYP21) in more than 90% of affected patients. The CYP21 gene is located within the HLA complex locus on chromosome 6 (6p21.3). During a molecular characterisation study of a group of 47 Mexican families with 21-hydroxylase deficiency, we identified nine in which the mutation or mutations found in the patient did not appear to originate from one of the parents. Through DNA fingerprinting, paternity was established in all nine families with a probability of non-paternity in the range of 10(-19) to 10(-23). Among these families, we identified one patient with exclusive paternal inheritance of all eight markers tested on chromosome 6p, despite normal maternal and paternal contributions for eight additional markers on three different chromosomes. We did not identify duplication of paternal information for markers in the 6q region, consistent with lack of expression of transient neonatal diabetes owing to genomic imprinting in this patient. Our results substantiate evidence for the existence of different genetic mechanisms involved in the expression of this recessive condition in a substantial portion (approximately 19%) of affected Mexican families. In addition to the identification of a patient with paternal uniparental disomy, the occurrence of germline mutations may explain the unusual pattern of segregation in the majority of the remaining eight families.
ISSN:0022-2593
1468-6244
1468-6244
DOI:10.1136/jmg.35.12.1014