• PMID: 8855822
• Gene Name: DAX1
• Condition: X-linkedadrenal hypoplasia congenita
• Association: The 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.
• Mutation: Q395X, nonsense mutation at position 91 (Y91X), 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), nonsense mutation at position 271 (Y271X), 1-base
• Population size: 6
• Population details: 6 patients with AHC
• Sex: Male, female
• Infertility type: Male infertility, Female infertility
• Other associated phenotypes: X-linkedadrenal hypoplasia congenita

Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita

Nakae J, Tajima T, Kusuda S, Kohda N, Okabe T, Shinohara N, Kato M, Murashita M, Mukai T, Imanaka K, Fujieda K.

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. FAU - Nakae, J AU - Nakae J AD - Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan. FAU - Tajima, T AU - Tajima T FAU - Kusuda, S AU - Kusuda S FAU - Kohda, N AU - Kohda N FAU - Okabe, T AU - Okabe T FAU - Shinohara, N AU - Shinohara N FAU - Kato, M AU - Kato M FAU - Murashita, M AU - Murashita M FAU - Mukai, T AU - Mukai T FAU - Imanaka, K AU - Imanaka K