Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita
| العنوان: | Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita |
|---|---|
| المؤلفون: | T Okabe, Mikiko Kato, Kohda N, Kusuda S, Mari Murashita, T Mukai, Toshihiro Tajima, Nozomi Shinohara, Kenji Fujieda, K Imanaka, Jun Nakae |
| المصدر: | The Journal of Clinical Endocrinology & Metabolism. 81:3680-3685 |
| بيانات النشر: | The Endocrine Society, 1996. |
| سنة النشر: | 1996 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1945-7197 0021-972X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d8fda4950a47d3e61e3fb745037467aTest https://doi.org/10.1210/jcem.81.10.8855822Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8d8fda4950a47d3e61e3fb745037467a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457197 0021972X |
|---|