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- Title
Truncation at the C-Terminus of the DAX-1 Protein Impairs Its Biological Actions in Patients with X-Linked Adrenal Hypoplasia Congenita.
- Authors
JUN NAKAE; TOSHIHIRO TAJIMA; SATOSHI KUSUDA; NAOYA KOHDA; TAKASHI OKABE; NOZOMI SHINOHARA; MIKIKO KATO; MAR1 MURASHITA; TOKUO MUKAI; KAORI IMANAKA; KENJI FUJIEDA
- Abstract
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.
- Publication
Journal of Clinical Endocrinology & Metabolism, 1996, Vol 81, Issue 10, p3680
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/jcem.81.10.8855822