{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T15:59:23Z","timestamp":1757779163742},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,6,25]],"date-time":"2004-06-25T00:00:00Z","timestamp":1088121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:p>This article reports the case of a boy diagnosed at 1.8 years of age with congenital adrenal hyperplasia due to 11 \u03b2\u2010hydroxylase deficiency. The patient showed salt\u2010wasting episodes during the neonatal period. On molecular analysis, a homozygous deletion hybrid (<jats:italic>CYP11B2<\/jats:italic>\u2013<jats:italic>CYP11B1<\/jats:italic>) involving the <jats:italic>CYP11B<\/jats:italic> locus at 8q24.3 was found. Southern blot analysis showed the break point of the chimera gene to be located before intron 5; sequence analysis identified it at exon 4 between codons 202 and 248. This <jats:italic>CYP11B2<\/jats:italic>(5\u2032)\/<jats:italic>B1<\/jats:italic>(3\u2032) hybrid should lack aldosterone synthase activity (due to the <jats:italic>CYP11B1<\/jats:italic> residues at exons 5 and 6), and the enzyme it codes for should not be promoted by adrenocorticotropic hormone (ACTH) (<jats:italic>CYP11B2<\/jats:italic> promoter sequences). The patient phenotype \u2013 neonatal salt\u2010wasting and 11 \u03b2\u2010hydroxylase deficiency \u2013 is in agreement with this hybrid structure. This is the first time a homozygous deletion hybrid generated by unequal crossover has been described in exon 4. This genetic lesion appears to be the reciprocal product from the recombination event that causes glucocorticoid\u2010remediable aldosteronism, a duplication dominant allele (<jats:italic>CYP11B2<\/jats:italic>\u2013<jats:italic>CYP11B1<\/jats:italic>\/<jats:italic>B2<\/jats:italic>\u2013<jats:italic>CYP11B1<\/jats:italic>) coding for additional aldosterone synthase activity regulated by ACTH. The clinical presentation of the condition in this patient contributes to the <jats:italic>in vivo<\/jats:italic> understanding of the regulation of this complex locus in which two \u2018duplicated\u2019 genes have evolved different regulatory and enzymatic activities involved in mineralocorticoid and glucocorticoid synthesis in the adrenal glands. The fact that this allele was first predicted and has now been documented clinically and molecularly <jats:italic>in vivo<\/jats:italic> is particularly noteworthy.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2004.00291.x","type":"journal-article","created":{"date-parts":[[2004,8,20]],"date-time":"2004-08-20T15:58:22Z","timestamp":1093017502000},"page":"229-235","source":"Crossref","is-referenced-by-count":15,"title":["Neonatal salt\u2010wasting and 11 \u03b2\u2010hydroxylase deficiency in a child carrying a homozygous deletion hybrid <i>CYP11B2<\/i> (aldosterone synthase)\u2013<i>CYP11B1<\/i> (11 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