{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:58:52Z","timestamp":1789955932002,"version":"4.0.1"},"reference-count":11,"publisher":"American Academy of Pediatrics (AAP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:p>We report the case of a 15-year-old girl who presented to a pediatric endocrinology clinic for delayed puberty with no signs of secondary sexual development. Her past medical history was significant for bilateral colobomas, inner-ear anomalies, hearing loss, and anosmia. Genetic testing revealed a novel de novo mutation in the CHD7 gene, one of the causative genes in CHARGE syndrome (coloboma, heart disease, choanal atresia, retarded growth and development and\/or central nervous system anomalies, genital anomalies and\/or hypogonadism, and ear anomalies and\/or deafness). We review the distinction between hypogonadotrophic hypogonadism and hypergonadotrophic hypogonadism and discuss the availability of molecular genetic testing for idiopathic hypogonadotrophic hypogonadism. CHD7 mutations have also been found in some patients with Kallmann syndrome, hypogonadotrophic hypogonadism, and anosmia, and we discuss the overlap between this syndrome and CHARGE syndrome. With the increased availability of genetic testing for a variety of disorders, it is important for pediatricians to become familiar with interpreting genetic test results. Finally, we illustrate that Bayes' theorem is a useful statistical tool for interpreting novel missense mutations of unknown significance.<\/jats:p>","DOI":"10.1542\/peds.2010-0164","type":"journal-article","created":{"date-parts":[[2010,11,2]],"date-time":"2010-11-02T03:53:25Z","timestamp":1288670005000},"page":"e1594-e1598","source":"Crossref","is-referenced-by-count":19,"title":["Delayed Puberty Due to a Novel Mutation in <i>CHD7<\/i> Causing CHARGE Syndrome"],"prefix":"10.1542","volume":"126","author":[{"given":"Andrew","family":"Dauber","sequence":"first","affiliation":[{"name":"Divisions of Endocrinology and"},{"name":"Clinical Investigator Training Program, Harvard\/MIT Health Sciences and Technology-Beth Israel Deaconess Medical Center, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel N.","family":"Hirschhorn","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology and"},{"name":"Genetics and"},{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts;"},{"name":"Broad Institute, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Picker","sequence":"additional","affiliation":[{"name":"Genetics and"},{"name":"Department of Child Psychiatry, Children's Hospital Boston, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Maher","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubrey","family":"Milunsky","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2010,12,1]]},"reference":[{"key":"2021121007004303900_B1","first-page":"969","article-title":"Puberty: ontogeny, neuroendocrinology, physiology, and disorders","volume-title":"Williams Textbook of Endocrinology","author":"Styne","year":"2008"},{"issue":"4","key":"2021121007004303900_B2","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/j.1365-2265.2009.03687.x","article-title":"The recent genetics of hypogonadotrophic hypogonadism: novel insights and new questions","volume":"72","author":"Semple","year":"2010","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"10","key":"2021121007004303900_B3","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nrendo.2009.177","article-title":"The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism","volume":"5","author":"Bianco","year":"2009","journal-title":"Nat Rev Endocrinol"},{"key":"2021121007004303900_B4","unstructured":"Lalani\u2008SR, Hefner\u2008MA, Belmont\u2008JW, Davenport\u2008SL. CHARGE syndrome. Available at: www.ncbi.nlm.nih.gov\/bookshelf\/br.fcgi?book=gene&part=charge. Accessed January 23, 2009"},{"issue":"3","key":"2021121007004303900_B5","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/ajmg.a.30559","article-title":"Updated diagnostic criteria for CHARGE syndrome: a proposal","volume":"133A","author":"Verloes","year":"2005","journal-title":"Am J Med Genet A"},{"issue":"10","key":"2021121007004303900_B6","doi-asserted-by":"crossref","first-page":"5621","DOI":"10.1210\/jc.2004-2474","article-title":"CHARGE syndrome includes hypogonadotropic hypogonadism and abnormal olfactory bulb development","volume":"90","author":"Pinto","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2021121007004303900_B7","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/1096-8628(20000918)94:3<228::AID-AJMG8>3.0.CO;2-H","article-title":"Hypogonadism and CHARGE association","volume":"94","author":"Wheeler","year":"2000","journal-title":"Am J Med Genet"},{"issue":"9","key":"2021121007004303900_B8","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/ng1407","article-title":"Mutations in a new member of the chromodomain gene family cause CHARGE syndrome","volume":"36","author":"Vissers","year":"2004","journal-title":"Nat Genet"},{"issue":"2","key":"2021121007004303900_B9","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1086\/500273","article-title":"Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation","volume":"78","author":"Lalani","year":"2006","journal-title":"Am J Hum Genet"},{"issue":"1","key":"2021121007004303900_B10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1399-0004.2008.01107.x","article-title":"CHD7 mutations in patients initially diagnosed with Kallmann syndrome: the clinical overlap with CHARGE syndrome","volume":"75","author":"Jongmans","year":"2009","journal-title":"Clin Genet"},{"issue":"4","key":"2021121007004303900_B11","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.ajhg.2008.09.005","article-title":"Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome","volume":"83","author":"Kim","year":"2008","journal-title":"Am J Hum Genet"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/126\/6\/e1594\/1055569\/zpe012100e1594.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/126\/6\/e1594\/1055569\/zpe012100e1594.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T16:11:51Z","timestamp":1639152711000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/126\/6\/e1594\/65007\/Delayed-Puberty-Due-to-a-Novel-Mutation-in-CHD7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12,1]]},"references-count":11,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2010,12,1]]},"published-print":{"date-parts":[[2010,12,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2010-0164","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,12,1]]}}}