{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:30:49Z","timestamp":1790195449586,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,12,28]],"date-time":"2013-12-28T00:00:00Z","timestamp":1388188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Arboleda <jats:italic>et\u00a0al<\/jats:italic>. have recently shown that <jats:styled-content style=\"fixed-case\">IMAG<\/jats:styled-content>e (intra\u2010uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities) syndrome is caused by gain\u2010of\u2010function mutations of maternally expressed gene <jats:italic><jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>1C<\/jats:italic> on chromosome 11p15.5. However, there is no other report describing clinical findings in patients with molecularly studied <jats:styled-content style=\"fixed-case\">IMAG<\/jats:styled-content>e syndrome. Here, we report clinical and molecular findings in Japanese patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>We studied a 46,<jats:styled-content style=\"fixed-case\">XX<\/jats:styled-content> patient aged 8\u00b75\u00a0years (case 1) and two 46,<jats:styled-content style=\"fixed-case\">XY<\/jats:styled-content> patients aged 16\u00b75 and 15\u00b70\u00a0years (cases 2 and 3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clinical studies revealed not only <jats:styled-content style=\"fixed-case\">IMAG<\/jats:styled-content>e syndrome\u2010compatible phenotypes in cases 1\u20133, but also hitherto undescribed findings including relative macrocephaly and apparently normal pituitary\u2010gonadal endocrine function in cases 1\u20133, familial glucocorticoid deficiency (<jats:styled-content style=\"fixed-case\">FGD<\/jats:styled-content>)\u2010like adrenal phenotype and the history of oligohydramnios in case 2, and arachnodactyly in case 3. Sequence analysis of <jats:italic><jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>1C<\/jats:italic>, pyrosequencing\u2010based methylation analysis of Kv<jats:styled-content style=\"fixed-case\">DMR<\/jats:styled-content>1 and high\u2010density oligonucleotide array comparative genome hybridization analysis for chromosome 11p15.5 were performed, showing an identical <jats:italic>de novo<\/jats:italic> and maternally inherited <jats:italic><jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>1C<\/jats:italic> gain\u2010of\u2010function mutation (p.Asp274Asn) in cases 1 and 2, respectively, and no demonstrable abnormality in case 3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of cases 1 and 2 with <jats:italic><jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>1C<\/jats:italic> mutation would argue the following: [1] relative macrocephaly is consistent with maternal expression of <jats:italic><jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>1C<\/jats:italic> in most tissues and biparental expression of <jats:italic><jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>1C<\/jats:italic> in the foetal brain; [2] <jats:styled-content style=\"fixed-case\">FGD<\/jats:styled-content>\u2010like phenotype can result from <jats:italic><jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>1C<\/jats:italic> mutation; and [3] genital abnormalities may primarily be ascribed to placental dysfunction. Furthermore, lack of <jats:italic><jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>1C<\/jats:italic> mutation in case 3 implies genetic heterogeneity in <jats:styled-content style=\"fixed-case\">IMAG<\/jats:styled-content>e syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12379","type":"journal-article","created":{"date-parts":[[2013,12,7]],"date-time":"2013-12-07T14:28:43Z","timestamp":1386426523000},"page":"706-713","source":"Crossref","is-referenced-by-count":16,"title":["<scp>IMAG<\/scp>e syndrome: clinical and genetic implications based on investigations in three Japanese patients"],"prefix":"10.1111","volume":"80","author":[{"given":"Fumiko","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Pediatrics Hamamatsu University School of Medicine Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Hamajima","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism Aichi Children's Health and Medical Center Obu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonobu","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Amano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Horikawa","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Radiology Tokyo Metropolitan Children's Medical Center Fuchu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hamamatsu University School of Medicine Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Fuke","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology National Research Institute for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichirou","family":"Sano","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology National Research Institute for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Fukami","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology National Research Institute for Child Health and Development Tokyo 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