Scientific letter
X-linked adrenal hypoplasia congenita: Novel missense mutation of DAX-1 gene
Hipoplasia adrenal congénita ligada al cromosoma X: mutación missense de novo en el gen DAX-1
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AHC is characterized by adrenal insufficiency in male children in the neonatal period or in early infancy.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> In addition, hypogonadotropic hypogonadism (HH) can be manifested at the time of puberty. Infertility due to HH and intrinsic failure in spermatogenesis<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> are commonly associated with X-linked AHC. Nevertheless the age and the way of presentation are quite variable,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> even in the same family, without a clear correlation between genotype-phenotype.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">DAX1</span> gene (<span class="elsevierStyleItalic">NR0B1</span>) is located in X chromosome (Xp21) and is the only one linked to the pathology. This gene encodes a protein that inhibits the transcription of other genes and plays an important role in the development and function of the adrenal glands, the hypothalamus, the pituitary and the gonads. <span class="elsevierStyleItalic">DAX1</span> gene mutations cause 58% of primary adrenal insufficiency of unknown etiology in boys,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> once autoimmune, metabolic disorders (adrenoleukodystrophy) and steroidogenic defects (<span class="elsevierStyleItalic">CYP21A2</span>) are excluded; and 100% in males with HH and family history of adrenal failure.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> To date, over 120 point mutations have been described in <span class="elsevierStyleItalic">DAX1</span> gene. Most of them are <span class="elsevierStyleItalic">nonsense</span> and <span class="elsevierStyleItalic">frameshift</span><a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> mutations located throughout the entire gene, causing a non-functional DAX1 protein. <span class="elsevierStyleItalic">Missense</span> mutations,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,5</span></a> less frequent, usually present within the carboxyl-terminal region, encoding a different amino acid that results in a DAX1 protein with a partial function; this could explain the uncommon cases described on adults. In the same way, large deletions have been reported encompassing part or all of the gene. Contiguous genes could also be involved.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A prompt genetic diagnosis of AHC can generate a significant decrease in morbi-mortality, guarantees a hormone replacement and genetic counseling in relatives. It is necessary to exclude this clinical entity in patients presenting with a salt-losing syndrome of unknown etiology.</p><p id="par0020" class="elsevierStylePara elsevierViewall">We present the case of a male, the third child of non-consanguineous young parents, without any relevant family and obstetrician history. The patient was born to term, birthweight of 3.560<span class="elsevierStyleHsp" style=""></span>g, (Percentile (Pc) 57), and birth length of 52<span class="elsevierStyleHsp" style=""></span>cm (Pc 75). He turned up at 24 days of life with failure to thrive. No other symptoms were associated. Physical exam revealed a dystrophic appearance, 3.1% weight loss (3.450<span class="elsevierStyleHsp" style=""></span>g, Pc 13), length 52<span class="elsevierStyleHsp" style=""></span>cm (Pc 15), blood pressure was 78/48<span class="elsevierStyleHsp" style=""></span>mmHg, positive fold sign, cutaneous hyperpigmentation and normal external male genitalia. Biochemical findings were compatible with salt-losing syndrome: sodium 116<span class="elsevierStyleHsp" style=""></span>mEq/l, potassium 7.8<span class="elsevierStyleHsp" style=""></span>mEq/l, glucose 70<span class="elsevierStyleHsp" style=""></span>mg/dl, urea 40.6<span class="elsevierStyleHsp" style=""></span>mg/dl, creatinine 0.34<span class="elsevierStyleHsp" style=""></span>mg/dl, pH 7.39, bicarbonate 20.4<span class="elsevierStyleHsp" style=""></span>mmol/l. Hormonal study is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Ultrasound and nuclear magnetic resonance showed normal-sized adrenal glands. The anti-adrenocortical antibodies were negative and very-long-chain fatty acids were normal.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Based in these findings, the diagnosis of primary adrenal insufficiency was made. After treatment with hydrocortisone and fluorhydrocortisone, the growth was normalized and the evolution was favorable. The possible association with HH implies a close monitoring during pubertal development to evaluate the need of pubertal induction and long-term sex steroid replacement.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Genetic testing was performed for <span class="elsevierStyleItalic">DAX1</span> gene, by complete genetic screening (Sanger sequencing) of the coding sequence of <span class="elsevierStyleItalic">DAX1</span>, revealing a <span class="elsevierStyleItalic">missense</span> mutation in hemicigosis of the variant c.773C>A in the gene <span class="elsevierStyleItalic">DAX1</span>, which substitutes Alanine amino acid for Aspartic in position 258 of the protein (p. A258D). This variant has not been previously described, nor appears in any of the consulted databases. The predictive bioinformatics analysis attributes a very likely pathogenic character. Although the variant is not found in the carboxy-terminal region, its result is likely to be a non-functional protein. This mutation was not found in the patient's mother, suggesting that she was not a carrier, so a <span class="elsevierStyleItalic">de novo</span> origin is assumed in the affected patient, with the consequent minimum risk of disease for other family members.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Domínguez García Á, Santana Rodríguez A, Cabrera Guedes MF. Hipoplasia adrenal congénita ligada al cromosoma X: mutación <span class="elsevierStyleItalic">missense de novo</span> en el gen <span class="elsevierStyleItalic">DAX-1</span>. Med Clin (Barc). 2019;152:242–243.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">mcg: micrograms; dl: deciliter; pg: picograms; ml: milliliter; ng: nanograms; DHEA-S: dehydroepiandrosterone-sulfate; ARP: plasma renin activity; h: hour.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hormonal levels \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Normal range \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cortisol (mcg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.7–19.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ACTH (pg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.654 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5–77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Delta4androstenedione (ng/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.6–3.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DHEA-S (mcg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80–560 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">17-hydroxyprogesterone (ng/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.53–1.83 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Testosterone (ng/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0–1.77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ARP (ng/ml/h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><32.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aldosterone (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">112 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25–315 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1985700.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hormonal levels.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and functional effects of mutations in the <span class="elsevierStyleItalic">DAX-1</span> gene in patients with adrenal hypoplasia congenita" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.T. Reutens" 1 => "J.C. Achermann" 2 => "M. Ito" 3 => "W.X. Gu" 4 => "R.L. Habiby" 5 => "P.A. Donohouse" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jcem.84.2.5468" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "1999" "volumen" => "84" "paginaInicial" => "504" "paginaFinal" => "511" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10022408" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinican and genetic heterogeneity of congenital adrenal hypoplasia due to NR0B1 gene mutations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Z. Landau" 1 => "A. Hanukoglu" 2 => "J. Sack" 3 => "N. Goldstein" 4 => "N. Weintrob" 5 => "A. Eliakim" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Endocrinol (Oxf)" "fecha" => "2010" "volumen" => "72" "paginaInicial" => "448" "paginaFinal" => "454" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">DAX1</span> and X-linked adrenal hypoplasia congenita: clinical and molecular analysis in five patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Mantovani" 1 => "E. de Menis" 2 => "G. Borretta" 3 => "G. Radetti" 4 => "S. Bondioni" 5 => "A. Spada" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1530/eje.1.02132" "Revista" => array:6 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "2006" "volumen" => "154" "paginaInicial" => "685" "paginaFinal" => "689" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16645015" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and molecular characterization of five Spanish kindreds with X-linked adrenal hypoplasia congénita: atypical findings and a novel mutation in <span class="elsevierStyleItalic">NR0B1</span>" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Rodríguez Estévez" 1 => "G. Pérez-Nanclares" 2 => "J. Fernández-Toral" 3 => "F. Rivas-Crespo" 4 => "J.P. López-Siguero" 5 => "I. Díez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1515/jpem-2014-0472" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Endocrinol Metab" "fecha" => "2015" "volumen" => "28" "paginaInicial" => "1129" "paginaFinal" => "1137" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26030781" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of <span class="elsevierStyleItalic">DAX1</span> (<span class="elsevierStyleItalic">NR0B1</span>) and steroidogenic factor-1 (<span class="elsevierStyleItalic">SF1/Ad4BP</span> NR5A1) in children and adults with primary adrenal failure: ten years’ experience" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Lin" 1 => "W.X. Gu" 2 => "G. Ozisik" 3 => "W.S. To" 4 => "C.J. Owen" 5 => "J.L. Jameson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Cin Endocrinol Metab" "fecha" => "2006" "volumen" => "91" "paginaInicial" => "3048" "paginaFinal" => "3054" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015200000006/v1_201903130923/S2387020619300518/v1_201903130923/en/main.assets" "Apartado" => array:4 [ "identificador" => "43311" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015200000006/v1_201903130923/S2387020619300518/v1_201903130923/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619300518?idApp=UINPBA00004N" ]
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