{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:36:56Z","timestamp":1770831416960,"version":"3.50.1"},"reference-count":28,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,11,1]]},"abstract":"<jats:p>The DAX-1 [DSS (dosage sensitive sex)-AHC critical region on the X, gene 1] gene is responsible for X-linked adrenal hypoplasia congenita (AHC). However, DAX-1 protein structure-function relationships are not well understood. Identification of missense mutations may help to reveal these relationships. We analyzed the DAX-1 gene from seven patients in six kindreds with X-linked AHC and identified one frameshift mutation, two missense mutations, and three deletion mutations. Case 1 had a 388delAG frameshift mutation, inducing a premature stop codon at position 70. Case 2 had a missense mutation, Lys382Asn, which encodes an asparagine (Asn) for lysine (Lys) at position 382. Sibling cases of 3-1 and 3-2 had a missense mutation of Trp291Cys, which encodes a substitution of cysteine (Cys) for tryptophan (Try) at position 291. The tryptophan (Trp) at position 291 and lysine (Lys) at position 382 in human DAX-1 protein are highly conserved among other related orphan nuclear receptor superfamily members. Cases 4, 5, and 6 showed deletion mutation. In case 6, a de novo deletion mutation was revealed by both southern hybridization and polymerase chain reaction (PCR) of a GGAA tetranucleotide tandem repeat. These findings suggest that: 1) Trp at position 291 and Lys at position 382, located in the C-terminal presumptive ligand binding domain, are important to the functional role of the DAX-1 protein in adrenal embryogenesis and\/or in hypothalamic-pituitary activity; and 2) molecular analysis of the DAX-1 gene may help genetic counseling, even in cases with deletion mutation, because a detection of de novo deletion may exclude another affected or carrier child.<\/jats:p>","DOI":"10.1210\/jcem.82.11.4342","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:01:10Z","timestamp":1389200470000},"page":"3835-3841","source":"Crossref","is-referenced-by-count":18,"title":["Three Novel Mutations and a De Novo Deletion Mutation of the DAX-1 Gene in Patients with X-Linked Adrenal Hypoplasia Congenita"],"prefix":"10.1210","volume":"82","author":[{"given":"Jun","family":"Nakae","sequence":"first","affiliation":[{"name":"Department of Pediatrics (J.N., S.A., T.T., N.S., M.M., K.F.), Hokkaido University School of Medicine, Sapporo 060;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (J.N., S.A., T.T., N.S., M.M., K.F.), Hokkaido University School of Medicine, Sapporo 060;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiro","family":"Tajima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (J.N., S.A., T.T., N.S., M.M., K.F.), Hokkaido University School of Medicine, Sapporo 060;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nozomi","family":"Shinohara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (J.N., S.A., T.T., N.S., M.M., K.F.), Hokkaido University School of Medicine, Sapporo 060;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari","family":"Murashita","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (J.N., S.A., T.T., N.S., M.M., K.F.), Hokkaido University School of Medicine, Sapporo 060;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Igarashi Pediatric Clinic (Y.I.), Sendai;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Kusuda","sequence":"additional","affiliation":[{"name":"Department of Neonatology (S.K.), Osaka City General Hospital, Osaka;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junzou","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (J.S.), Fukushima Prefectural Medical Collage, Fukushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Fujieda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (J.N., S.A., T.T., N.S., M.M., K.F.), Hokkaido University School of Medicine, Sapporo 060;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071618250732700_R1","author":"Migeon","year":"1994"},{"key":"2020071618250732700_R2","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/path.1700600220","article-title":"Addison\u2019s disease due to congenital hypoplasia of the adrenals in an infant aged 33 days.","volume":"60","year":"1948","journal-title":"J Path Bact"},{"key":"2020071618250732700_R3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1136\/bmj.1.4698.115","article-title":"Addison\u2019s disease occurring in two brothers","volume":"i","author":"Briggs","year":"1951","journal-title":"Br Med J."},{"key":"2020071618250732700_R4","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1001\/archpedi.1957.04030070108013","article-title":"Congenital adrenal hypoplasia: report of a case with the characteristic clinical features of desadrenocorticism and autopsy finding of extreme hypoplasia of the adrenal glands.","volume":"94","author":"Harlem","year":"1957","journal-title":"Amer J Dis Child"},{"key":"2020071618250732700_R5","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/S0140-6736(59)91020-7","article-title":"Congenital adrenal hypoplasia in siblings","volume":"i","author":"Mitchell","year":"1959","journal-title":"Lancet."},{"key":"2020071618250732700_R6","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1210\/jcem-19-6-726","article-title":"Addison\u2019s disease in two brothers.","volume":"19","author":"Meakin","year":"1959","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618250732700_R7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1136\/adc.35.184.561","article-title":"Adrenal cortical hypoplasia in siblings.","volume":"35","author":"Boyd","year":"1960","journal-title":"Arch Dis Child"},{"key":"2020071618250732700_R8","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1001\/archpedi.1966.02090050140014","article-title":"Addison\u2019s disease in childhood. 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