Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita
| Autor: | T Okabe, Mikiko Kato, Kohda N, Kusuda S, Mari Murashita, T Mukai, Toshihiro Tajima, Nozomi Shinohara, Kenji Fujieda, K Imanaka, Jun Nakae |
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| Rok vydání: | 1996 |
| Předmět: |
Adult
Male medicine.medical_specialty X Chromosome Adolescent Genetic Linkage Receptors Retinoic Acid Endocrinology Diabetes and Metabolism DNA Mutational Analysis Clinical Biochemistry Nonsense mutation Biology medicine.disease_cause Polymerase Chain Reaction Biochemistry Frameshift mutation Endocrinology Hypogonadotropic hypogonadism X-linked adrenal hypoplasia congenita Internal medicine medicine Humans Amino Acid Sequence RNA Messenger Gene X-linked recessive inheritance DNA Primers Genetics Mutation Base Sequence DAX-1 Orphan Nuclear Receptor Biochemistry (medical) Infant Sequence Analysis DNA medicine.disease DNA-Binding Proteins Repressor Proteins Child Preschool DAX1 Gene Deletion Adrenal Insufficiency Transcription Factors |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 81:3680-3685 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.81.10.8855822 |
| Popis: | The DAX-1 [DSS (dosage-sensitive sex)-AHC critical region in the X, gene 1] gene has been reported to be responsible for X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism. However, the function and structure of the DAX-1 protein have not been characterized. In this study, molecular analysis of the DAX-1 gene from 6 patients with AHC, including 2 siblings, identified 5 novel mutations with 3 nonsense mutations and 2 frameshift mutations. Case 1 had a nonsense mutation at position 395 (Q395X). Cases 2 and 3, who were siblings, had a nonsense mutation at position 91 (Y91X). Case 4 had a 2-base deletion (AT) at nucleotides 1610 and 1611 and a 1-base insertion (G) resulting in a premature stop codon at position 462 (1610-1611 del AT ins G). Case 5 had a nonsense mutation at position 271 (Y271X). Case 6 had a 1-base deletion (C) at nucleotide 1169, which induced a frame shift and a premature stop codon at position 371 (1169 del C). All mutated DAX-1 proteins had truncated C-terminal domains. In addition, reverse transcription-PCR and direct sequencing characterized the mutant messenger ribonucleic acid in testis from case 1. Our results suggest that these 5 novel mutations are responsible for X-linked AHC and that the C-terminus of the DAX-1 protein, especially the terminal 11 amino acids, is necessary for normal adrenal cortical embryogenesis. |
| Databáze: | OpenAIRE |
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