Similar articles

Abstract: congenital X-linked adrenal hypoplasia (AHC) is a rare disease characterized by primary adrenal insufficiency before adolescence and by hypogonadotropic hypogonadism (HHG) during adolescence. In this paper, we present a Chinese family with AHC. Two brothers, misdiagnosed with adrenal insufficiency of unknown etiology at the age of 9, were correctly diagnosed with AHC when delayed puberty, HHG, and testicular defects were observed. We investigated the clinical features and identified the dosage-sensitive sex reversal AHC critical region of the X chromosome gene 1 (DAX-1) mutation in this kindred. Direct sequencing of the DAX-1 gene revealed that the two siblings have a novel mutation (1268delA) of which their mother is a heterozygous carrier. This mutation causes a frameshift and a premature stop codon at position 436, encoding a truncated protein. It is important to increase knowledge of the mutational spectrum in genes related to this disease, linking phenotype to genotype.

伴DAX-1基因新突变的先天性肾上腺发育不良 家系报道

[1]Burke, B.A., Wick, M.R., King, R., et al., 1988. Congenital adrenal hypoplasia and selective absence of pituitary luteinizing hormone: a new autosomal recessive syndrome. Am. J. Med. Genet., 31(1):75-97.

[2]Chang, G.Y., Dong, Z.Y., Wang, W., et al., 2011. Analysis of clinical manifestations and gene mutations in children with primary adrenal insufficiency. J. Shanghai Jiaotong Univ. (Med. Sci.), 31(6):782-787 (in Chinese).

[3]Fu, Y., Nie, M., Xia, W.B., et al., 2010. Clinical features of 9 patients with X-linked adrenal hypoplasia congenita caused by DAX1/NR0B1 gene mutations. Nat. Med. J. China, 90(30):2119-2122 (in Chinese).

[4]Gong, Y.P., Xing, G., Wang, B.A., et al., 2009. Clinical and epigenetic study of a case with adrenal hypoplasia congenita caused by a novel DAX-1 gene mutation. Chin. J. Endocrinol. Metab., 25(1):62-63 (in Chinese).

[5]Guo, W., Burris, T.P., McCabe, E.R., 1995. Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/gonadal axis. Biochem. Mol. Med., 56(1):8-13.

[6]Guo, W., Burris, T.P., Zhang, Y.H., et al., 1996. Genomic sequence of the DAX1 gene: an orphan nuclear receptor responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab., 81(7):2481-2486.

[7]Ito, M., Yu, R., Jameson, J.L., 1997. DAX-1 inhibits SF-1-mediated transactivation via a carboxy-terminal domain that is deleted in adrenal hypoplasia congenita. Mol. Cell. Biol., 17(3):1476-1483.

[8]Iyer, A.K., McCabe, E.R., 2004. Molecular mechanisms of DAX1 action. Mol. Genet. Metab., 83(1-2):60-73.

[9]Li, N., Liu, R., Zhang, H.J., et al., 2010. Seven novel DAX-1 mutations with loss of function identified in Chinese patients with congenital adrenal hypoplasia. J. Clin. Endocrinol. Metab., 95(9):E104-E111.

[10]Muscatelli, F., Strom, T.M., Walker, A.P., et al., 1994. Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Nature, 372(6507):672-676.

[11]Phelan, J.K., McCabe, E.R., 2001. Mutations in NR0B1 (DAX1) and NR5A1 (SF1) responsible for adrenal hypoplasia congenita. Hum. Mutat., 18(6):472-487.

[12]Seminara, S.B., Hayes, F.J., Crowley, W.F.Jr., 1998. Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann’s syndrome): pathophysiological and genetic considerations. Endocr. Rev., 19(5):521-539.

[13]Tamai, K.T., Monaco, L., Alastalo, T.P., et al., 1996. Hormonal and developmental regulation of DAX-1 expression in Sertoli cells. Mol. Endocrinol., 10(12):1561-1569.

[14]Wang, D.P., Chen, C.R., Liu, Y.X., et al., 2011. One case of late-onset adrenal hypoplasia congenita caused by a novel mutation of DAX-1 gene. Chin. J. Endocrinol. Metab., 27(1):47-49 (in Chinese).

[15]Xiao, Y., Yang, J., Zhang, H.J., et al., 2007. Identification of a novel missense mutation of the DAX-1 gene in a Chinese pedigree with X-linked adrenal hypoplasia congenita. Chin. J. Pediatr., 45(12):937-941 (in Chinese).

[16]Xu, M., Wang, Y.M., Xing, X.N., et al., 2009. A novel mutation of 428delG in DAX-1 gene causing X-linked adrenal hypoplasia congenital. Chin. J. Med. Genet., 26(1):11-15 (in Chinese).

[17]Yang, J., Zhang, H.J., Xiao, Y., et al., 2007. DAX-1 gene deficiency in two cases with congenital adrenal hypoplasia. Chin. J. Endocrinol. Metab., 23(5):475-477 (in Chinese).

[18]Yu, R.N., Achermann, J.C., Ito, M., et al., 1998. The role of DAX-1 in reproduction. Trends Endocrinol. Metab., 9(5):169-175.

[19]Zanaria, E., Muscatelli, F., Bardoni, B., et al., 1994. An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita. Nature, 372(6507):635-641.

[20]Zhang, H.B., Nie, M., 2011. Clinical and molecular genetic analysis of a patient with adrenal hypoplasia congenital and hypogonadotropic hypogonadism. J. Reprod. Med., 20(3):183-187 (in Chinese).

[21]Zhou, J., Oakley, R.H., Cidlowski, J.A., 2008. DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X-chromosome, gene 1) selectively inhibits transactivation but not transrepression mediated by the glucocorticoid receptor in a LXXLL-dependent manner. Mol. Endocrinol., 22(7):1521-1534.