{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:08:03Z","timestamp":1753862883936,"version":"3.41.2"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Case Reports"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Isolated growth hormone deficiency (IGHD) IA is inherited autosomal recessively and occurs due to GH1 gene deletions. This study emphasizes the importance of clinical diagnosis and molecular examination for detecting novel mutations to prevent misdiagnosis and to consider timely and appropriate management of the current and long\u2010term consequences of the defect, such as additional deficiencies. We report a male infant who initially presented with a growth delay (\u20104SD) at 4\u2009months old, and at 16\u2009months old, was referred to our endocrinology department. Physical examination revealed developmental delay, macrocephaly, head lag, loose body, large head circumference, low and flat nasal bridge, forehead protuberance, three\u2010pronged fingers, shortness of the hands and feet joints, small palms and plantar, small penises, delayed tooth eruption, and disability to walk. His hormonal tests showed normal free T4 (14.08\u2009pmol\/L), upper limit TSH level (5.41\u2009\u03bcIU\/mL), normal random cortisol 8\u2009AM (250.53\u2009\u03bcg\/mL), mild high ACTH level (79.6\u2009pg\/mL), low IGF1 (13.0) and fasting GH (0.03\u2009ng\/mL). GH (ng\/mL) maximal response to the arginine test was &lt;\u20090.05. Whole Exome Sequencing, Polymerase Chain Reaction (PCR), and Quantitative Real\u2010Time PCR were performed on a peripheral blood sample obtained from the patient. The infant was found to have a homozygous large deletion of approximately 1.6\u2009kb spanning the GH1 gene, which contained exons 1\u20134 with an autosomal recessive inheritance and a heterozygous deletion of exons 1\u20134 of GH1 in the parents and homozygous wild\u2010type in the sibling. Novel mutations in the GH\u20101 gene cluster are considered an important cause of idiopathic congenital IGHD. As a result, the role of gene sequencing, besides considering clinical features, should not be neglected.<\/jats:p>","DOI":"10.1002\/ccr3.70234","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T06:19:02Z","timestamp":1740032342000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isolated Growth Hormone Deficiency <scp>IA<\/scp> due to a Novel Homozygous Large Deletion \u223c1.6\u2009kb Spanning Exons 1\u20134 of <scp>GH1<\/scp> Gene: A Case Report"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3248-7311","authenticated-orcid":false,"given":"Shahab","family":"Noorian","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology, School of Medicine Alborz University of Medical Sciences  Karaj Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hedieh","family":"Soltani","sequence":"additional","affiliation":[{"name":"Student Research Committee, School of Medicine Alborz University of Medical Sciences  Karaj Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatemeh","family":"Aghamahdi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, School of Medicine Alborz University of Medical Sciences  Karaj Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahram","family":"Savad","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Medicine Tehran University of Medical Sciences (TUMS)  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahnaz Seifi","family":"Alan","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center Alborz University of Medical Sciences  Karaj Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.147"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2010.06.007"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.4274\/jcrpe.v2i2.52"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2006.11.010"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ghir.2016.04.001"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199801000-00016"},{"issue":"3","key":"e_1_2_14_8_1","first-page":"480","article-title":"GH1 Gene Deletions and IGHD Type 1A","volume":"3","author":"Cogan J. D.","year":"2006","journal-title":"Pediatric Endocrinology Reviews: PER"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199205000-00026"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181a7e8f8"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.6084.427"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.65.11.1199"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-2783"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-011-0588-5"},{"key":"e_1_2_14_15_1","first-page":"A110","article-title":"A Frameshift Mutation Causing Isolated Growth Hormone Deficiency Type 1A","volume":"47","author":"Duquesnoy P.","year":"1990","journal-title":"American Journal of Human Genetics"},{"issue":"4","key":"e_1_2_14_16_1","first-page":"1247","article-title":"Screening for Growth Hormone (GH) Gene Splice\u2010Site Mutations in Sporadic Cases With Severe Isolated GH Deficiency Using Ectopic Transcript Analysis","volume":"80","author":"Binder G.","year":"1995","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"issue":"5","key":"e_1_2_14_17_1","first-page":"1224","article-title":"Heterogeneous Growth Hormone (GH) Gene Mutations in Familial GH Deficiency","volume":"76","author":"Cogan J. 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