{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:50:15Z","timestamp":1781106615942,"version":"3.54.1"},"reference-count":40,"publisher":"Japanese Society for Pediatric Endocrinology","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pediatr Endocrinol"],"published-print":{"date-parts":[[2023]]},"DOI":"10.1297\/cpe.2022-0061","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T18:10:06Z","timestamp":1667326206000},"page":"65-71","source":"Crossref","is-referenced-by-count":3,"title":["A case of syndromic congenital hypothyroidism with a 15.2 Mb interstitial          deletion on 2q12.3q14.2 involving &lt;i&gt;PAX8&lt;\/i&gt;"],"prefix":"10.1297","volume":"32","author":[{"given":"Megumi","family":"Iwahashi-Odano","sequence":"first","affiliation":[{"name":"Department of Molecular Endocrinology, National Research              Institute for Child Health and Development, Tokyo, Japan"},{"name":"Department of Pediatrics, The Jikei University School of              Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Kurume              University School of Medicine, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Narumi","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, National Research              Institute for Child Health and Development, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"125","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Delado\u00eby,                J,              B\u00e9langer, N,                Van Vliet,              G. Random            variability in congenital hypothyroidism from thyroid dysgenesis over 16 years in            Qu\u00e9bec. J Clin Endocrinol Metab          2007;92: 3158\u201361.","DOI":"10.1210\/jc.2007-0527"},{"key":"2","doi-asserted-by":"publisher","unstructured":"2. Plachov,              D, Chowdhury,                K, Walther,                C, Simon,                D, Guenet,                JL, Gruss,                P. Pax8, a            murine paired box gene expressed in the developing excretory system and thyroid            gland. Development          1990;110: 643\u201351.","DOI":"10.1242\/dev.110.2.643"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Kozmik,              Z, Kurzbauer,                R, D\u00f6rfler,                P,                Busslinger,              M. Alternative            splicing of Pax-8 gene transcripts is developmentally regulated and generates isoforms            with different transactivation properties. Mol Cell            Biol          1993;13: 6024\u201335.","DOI":"10.1128\/mcb.13.10.6024-6035.1993"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Narumi,              S, Muroya,                K, Asakura,                Y, Adachi,                M,              Hasegawa,            T. Transcription            factor mutations and congenital hypothyroidism: systematic genetic screening of a            population-based cohort of Japanese patients. J Clin Endocrinol            Metab          2010;95: 1981\u20135.","DOI":"10.1210\/jc.2009-2373"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Ramos,              HE, Carr\u00e9,                A,              Chevrier, L,                Szinnai, G,                Tron, E,                Cerqueira,              TL, et al.            Extreme phenotypic variability of thyroid dysgenesis in six new cases of            congenital hypothyroidism due to PAX8 gene loss-of-function mutations.            Eur J Endocrinol          2014;171: 499\u2013507.","DOI":"10.1530\/EJE-13-1006"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Macchia,                PE, Lapi,                P, Krude,                H, Pirro,                MT,              Missero, C,                Chiovato,            L, et al.            PAX8 mutations associated with congenital hypothyroidism caused by            thyroid dysgenesis. Nat Genet          1998;19: 83\u20136.","DOI":"10.1038\/ng0598-83"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Congdon,              T, Nguyen,                LQ,                Nogueira,              CR, Habiby,                RL,                Medeiros-Neto,              G, Kopp,                P. A novel            mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid            hypoplasia: evidence for phenotypic variability in mother and child.            J Clin Endocrinol Metab          2001;86: 3962\u20137.","DOI":"10.1210\/jcem.86.8.7765"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Vilain,              C, Rydlewski,                C, Duprez,                L,                Heinrichs,              C,              Abramowicz,            M, Malvaux,                P, et al.            Autosomal dominant transmission of congenital thyroid hypoplasia due to            loss-of-function mutation of PAX8. J Clin Endocrinol            Metab          2001;86: 234\u20138.","DOI":"10.1210\/jc.86.1.234"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. de                Sanctis, L,                Corrias, A,                Romagnolo,              D, Di Palma,                T, Biava,                A,                Borgarello,              G, et al.            Familial PAX8 small deletion (c.989_992delACCC) associated with extreme            phenotype variability. J Clin Endocrinol Metab          2004;89: 5669\u201374.","DOI":"10.1210\/jc.2004-0398"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Meeus,              L, Gilbert,                B,                Rydlewski,              C, Parma,                J, Roussie,                AL,                Abramowicz,              M, et al.            Characterization of a novel loss of function mutation of PAX8 in a            familial case of congenital hypothyroidism with in-place, normal-sized            thyroid. J Clin Endocrinol Metab          2004;89: 4285\u201391.","DOI":"10.1210\/jc.2004-0166"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Grasberger,                H,                Ringkananont,              U,              Lefrancois,            P, Abramowicz,                M, Vassart,                G,              Refetoff,            S. Thyroid            transcription factor 1 rescues PAX8\/p300 synergism impaired by a natural PAX8 paired            domain mutation with dominant negative activity. Mol            Endocrinol          2005;19: 1779\u201391.","DOI":"10.1210\/me.2004-0426"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Al                Taji, E,                Biebermann,              H, L\u00edmanov\u00e1,                Z, Hn\u00edkov\u00e1,                O, Zikmund,                J, Dame,                C, et al.            Screening for mutations in transcription factors in a Czech cohort of 170            patients with congenital and early-onset hypothyroidism: identification of a novel PAX8            mutation in dominantly inherited early-onset non-autoimmune            hypothyroidism. Eur J Endocrinol          2007;156: 521\u20139.","DOI":"10.1530\/EJE-06-0709"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Di                Palma, T,                Zampella,            E, Filippone,                MG,              Macchia, PE,                Ris-Stalpers,              C, de Vroede,                M, et al.            Characterization of a novel loss-of-function mutation of PAX8 associated            with congenital hypothyroidism. Clin Endocrinol (Oxf)          2010;73: 808\u201314.","DOI":"10.1111\/j.1365-2265.2010.03851.x"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Jo,                W, Ishizu,                K, Fujieda,                K, Tajima,                T. Congenital            hypothyroidism caused by a PAX8 gene mutation manifested as sodium\/Iodide symporter gene            defect. J Thyroid Res          2010;2010: 619013.","DOI":"10.4061\/2010\/619013"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Narumi,              S, Yoshida,                A, Muroya,                K, Asakura,                Y, Adachi,                M,              Fukuzawa, R,              et al. PAX8 mutation disturbing thyroid            follicular growth: a case report. J Clin Endocrinol            Metab          2011;96: E2039\u201344.","DOI":"10.1210\/jc.2011-1114"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Narumi,              S, Araki,                S, Hori,                N, Muroya,                K,              Yamamoto, Y,                Asakura, Y,              et al. Functional characterization of four            novel PAX8 mutations causing congenital hypothyroidism: new evidence for            haploinsufficiency as a disease mechanism. Eur J            Endocrinol          2012;167: 625\u201332.","DOI":"10.1530\/EJE-12-0410"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Carvalho,                A,              Hermanns, P,                Rodrigues,              AL, Sousa,                I, Anselmo,                J, Bikker,                H, et al.            A new PAX8 mutation causing congenital hypothyroidism in three            generations of a family is associated with abnormalities in the urogenital            tract. Thyroid          2013;23: 1074\u20138.","DOI":"10.1089\/thy.2012.0649"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Hermanns,                P,                Grasberger,              H, Cohen,                R,              Freiberg, C,                D\u00f6rr, HG,                Refetoff,            S, et al.            Two cases of thyroid dysgenesis caused by different novel PAX8 mutations            in the DNA-binding region: in vitro studies reveal different pathogenic            mechanisms. Thyroid          2013;23: 791\u20136.","DOI":"10.1089\/thy.2012.0141"},{"key":"19","unstructured":"19. Zou,              H, Chai,                J, Liu,                S, Zang,                H, Yu,                X, Tian,                L, et al.            A De novo PAX8 mutation in a Chinese child with congenital thyroid            dysgenesis. Int J Clin Exp Pathol          2015;8: 11434\u20139."},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. L\u00f6f,              C, Patyra,                K,                Kuulasmaa,              T,                Vangipurapu,              J, Undeutsch,                H,              Jaeschke, H,              et al. Detection of novel gene variants            associated with congenital hypothyroidism in a finnish patient cohort.            Thyroid          2016;26: 1215\u201324.","DOI":"10.1089\/thy.2016.0016"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Srichomkwun,                P, Admoni,                O,              Refetoff, S,                de Vries,            L. A novel            mutation (S54C) of the PAX8 gene in a family with congenital hypothyroidism and a high            proportion of affected individuals. Horm Res Paediatr          2016;86: 137\u201342.","DOI":"10.1159\/000445891"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Qian,              F, Li,                GY, Wu,                XJ, Jia,                Q, Lyu,                GT, Wang,                ML, et al.            Novel non-synonymous mutations of PAX8 in a cohort of Chinese with            congenital hypothyroidism. Chin Med J (Engl)          2019;132: 1322\u20137.","DOI":"10.1097\/CM9.0000000000000213"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Komatsu,              M, Takahashi,                T,                Takahashi,              I, Nakamura,                M,                Takahashi,              I, Takada,                G. Thyroid            dysgenesis caused by PAX8 mutation: the hypermutability with CpG dinucleotides at codon            31. J Pediatr          2001;139: 597\u20139.","DOI":"10.1067\/mpd.2001.117071"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Iwahashi-Odano,                M,              Fujisawa, Y,                Ogata, T,                Nakashima,              S, Muramatsu,                M, Narumi,                S.            Identification and functional characterization of a novel              <i>PAX8<\/i> mutation (p.His39Pro) causing familial thyroid            hypoplasia. Clin Pediatr Endocrinol          2020;29: 173\u20138.","DOI":"10.1297\/cpe.29.173"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Iwahashi-Odano,                M,              Nagasaki, K,                Fukami, M,                Nishioka,            J, Yatsuga,                S, Asakura,                Y, et al.            Congenital hypothyroidism due to truncating PAX8 mutations: a case series            and molecular function studies. J Clin Endocrinol Metab          2020;105: 11.","DOI":"10.1210\/clinem\/dgaa584"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Ma,                D, Marion,                R, Punjabi,                NP,              Pereira, E,                Samanich,            J, Agarwal,                C, et al.            A de novo 10.79 Mb interstitial deletion at 2q13q14.2 involving PAX8            causing hypothyroidism and mullerian agenesis: a novel case report and literature            review. Mol Cytogenet          2014;7: 85.","DOI":"10.1186\/s13039-014-0085-4"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27. Smol,              T,                Ribero-Karrouz,              W, Edery,                P, Gorduza,                DB,                Catteau-Jonard,              S,                Manouvrier-Hanu,              S, et al.            Mayer-Rokitansky-K\u00fcnster-Hauser syndrome due to 2q12.1q14.1 deletion:            PAX8 the causing gene? Eur J Med Genet          2020;63: 103812.","DOI":"10.1016\/j.ejmg.2019.103812"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28. Ohnishi,              H, Inomata,                H,              Watanabe, T,                Wataki, K,                Sato, H,                Sanayama,            K, et al.            Clinical utility of thyroid ultrasonography in the diagnosis of            congenital hypothyroidism. Endocr J          2002;49: 293\u20137.","DOI":"10.1507\/endocrj.49.293"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29. Hladilkova,                E, Bar\u00f8y,                T,              Fannemel, M,                Vallova, V,                Misceo, D,                Bryn, V,              et al. A recurrent deletion on chromosome            2q13 is associated with developmental delay and mild facial          dysmorphisms. Mol Cytogenet          2015;8: 57.","DOI":"10.1186\/s13039-015-0157-0"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30. Friedrichsen,                S, Christ,                S, Heuer,                H, Sch\u00e4fer,                MK, Parlow,                AF, Visser,                TJ, et al.            Expression of pituitary hormones in the Pax8-\/- mouse model of congenital            hypothyroidism. Endocrinology          2004;145: 1276\u201383.","DOI":"10.1210\/en.2003-1227"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31. Zhu,              X,              Gleiberman,              AS,              Rosenfeld,            MG. Molecular            physiology of pituitary development: signaling and transcriptional            networks. Physiol Rev          2007;87: 933\u201363.","DOI":"10.1152\/physrev.00006.2006"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32. Gustavsson,                P,                Schoumans,              J, Staaf,                J, J\u00f6nsson,                G,              Carlsson, F,                Kristoffersson,              U, et al.            Hemizygosity for chromosome 2q14.2-q22.1 spanning the GLI2 and PROC genes            associated with growth hormone deficiency, polydactyly, deep vein thrombosis and            urogenital abnormalities. Clin Genet          2006;69: 441\u20133.","DOI":"10.1111\/j.1399-0004.2006.00601.x"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33. Kevelam,                SH, van                Harssel, JJ,                van der Zwaag,              B, Smeets,                HJ,                Paulussen,              AD,                Lichtenbelt,              KD. A patient            with a mild holoprosencephaly spectrum phenotype and heterotaxy and a 1.3\u2009Mb deletion            encompassing GLI2. Am J Med Genet A          2012;158A: 166\u201373.","DOI":"10.1002\/ajmg.a.34350"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34. Solomon,                BD,                Pineda-Alvarez,              DE, Gropman,                AL, Willis,                MJ, Hadley,                DW, Muenke,                M. High            intellectual function in individuals with mutation-positive microform            holoprosencephaly. Mol Syndromol          2012;3: 140\u20132.","DOI":"10.1159\/000341373"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35. Gregory,                LC,                Gaston-Massuet,              C,              Andoniadou,              CL, Carreno,                G, Webb,                EA,                Kelberman,              D, et al.            The role of the sonic hedgehog signalling pathway in patients with            midline defects and congenital hypopituitarism. Clin Endocrinol            (Oxf)          2015;82: 728\u201338.","DOI":"10.1111\/cen.12637"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36. Goumy,              C,                Gay-Bellile,              M, Salaun,                G, Kemeny,                S,                Eymard-Pierre,              E, Biard,                M, et al.            A novel 2q14.1q14.3 deletion involving GLI2 and RNU4ATAC genes associated            with partial corpus callosum agenesis and severe intrauterine growth            retardation. Birth Defects Res A Clin Mol Teratol          2016;106: 793\u20137.","DOI":"10.1002\/bdra.23535"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37. Korda\u00df,              U, Schr\u00f6der,                C,              Elbracht, M,                Soellner,            L, Eggermann,                T. A familial            GLI2 deletion (2q14.2) not associated with the holoprosencephaly syndrome            phenotype. Am J Med Genet A          2015;167A: 1121\u20134.","DOI":"10.1002\/ajmg.a.36972"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38. Oikonomakis,                V, Kosma,                K,              Mitrakos, A,                Sofocleous,              C,              Pervanidou,            P, Syrmou,                A, et al.            Recurrent copy number variations as risk factors for autism spectrum            disorders: analysis of the clinical implications. Clin            Genet          2016;89: 708\u201318.","DOI":"10.1111\/cge.12740"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39. Elizabeth,                MSM,                Verkerk,              AJMH,                Hokken-Koelega,              ACS, Verlouw,                JAM,                Argente, J,                Pfaeffle,            R, et al.            Unique near-complete deletion of GLI2 in a patient with combined            pituitary hormone deficiency and post-axial polydactyly. Growth            Horm IGF Res          2020;50: 35\u201341.","DOI":"10.1016\/j.ghir.2019.10.002"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40. Elward,              C, Berg,                J, Oberlin,                JM, Rohena,                L. A case            series of a mother and two daughters with a <i>GLI2<\/i> gene deletion            demonstrating variable expressivity and incomplete penetrance.            Clin Case Rep          2020;8: 2138\u201344.","DOI":"10.1002\/ccr3.3085"}],"container-title":["Clinical Pediatric Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/cpe\/32\/1\/32_2022-0061\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T01:21:46Z","timestamp":1715304106000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/cpe\/32\/1\/32_2022-0061\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.1297\/cpe.2022-0061","relation":{},"ISSN":["0918-5739","1347-7358"],"issn-type":[{"value":"0918-5739","type":"print"},{"value":"1347-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023]]},"article-number":"2022-0061"}}