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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Turner syndrome presented with tall stature due to overdosage of the <italic>SHOX</italic> gene</title><author><name sortKey="Seo, Go Hun" sort="Seo, Go Hun" uniqKey="Seo G" first="Go Hun" last="Seo">Go Hun Seo</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Kang, Eungu" sort="Kang, Eungu" uniqKey="Kang E" first="Eungu" last="Kang">Eungu Kang</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Cho, Ja Hyang" sort="Cho, Ja Hyang" uniqKey="Cho J" first="Ja Hyang" last="Cho">Ja Hyang Cho</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Lee, Beom Hee" sort="Lee, Beom Hee" uniqKey="Lee B" first="Beom Hee" last="Lee">Beom Hee Lee</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Choi, Jin Ho" sort="Choi, Jin Ho" uniqKey="Choi J" first="Jin-Ho" last="Choi">Jin-Ho Choi</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Kim, Gu Hwan" sort="Kim, Gu Hwan" uniqKey="Kim G" first="Gu-Hwan" last="Kim">Gu-Hwan Kim</name><affiliation><nlm:aff id="A2">Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Seo, Eul Ju" sort="Seo, Eul Ju" uniqKey="Seo E" first="Eul-Ju" last="Seo">Eul-Ju Seo</name><affiliation><nlm:aff id="A2">Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Yoo, Han Wook" sort="Yoo, Han Wook" uniqKey="Yoo H" first="Han-Wook" last="Yoo">Han-Wook Yoo</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26191517</idno><idno type="pmc">4504991</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504991</idno><idno type="RBID">PMC:4504991</idno><idno type="doi">10.6065/apem.2015.20.2.110</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000174</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000174</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Turner syndrome presented with tall stature due to overdosage of the <italic>SHOX</italic> gene</title><author><name sortKey="Seo, Go Hun" sort="Seo, Go Hun" uniqKey="Seo G" first="Go Hun" last="Seo">Go Hun Seo</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Kang, Eungu" sort="Kang, Eungu" uniqKey="Kang E" first="Eungu" last="Kang">Eungu Kang</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Cho, Ja Hyang" sort="Cho, Ja Hyang" uniqKey="Cho J" first="Ja Hyang" last="Cho">Ja Hyang Cho</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Lee, Beom Hee" sort="Lee, Beom Hee" uniqKey="Lee B" first="Beom Hee" last="Lee">Beom Hee Lee</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Choi, Jin Ho" sort="Choi, Jin Ho" uniqKey="Choi J" first="Jin-Ho" last="Choi">Jin-Ho Choi</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Kim, Gu Hwan" sort="Kim, Gu Hwan" uniqKey="Kim G" first="Gu-Hwan" last="Kim">Gu-Hwan Kim</name><affiliation><nlm:aff id="A2">Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Seo, Eul Ju" sort="Seo, Eul Ju" uniqKey="Seo E" first="Eul-Ju" last="Seo">Eul-Ju Seo</name><affiliation><nlm:aff id="A2">Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author><author><name sortKey="Yoo, Han Wook" sort="Yoo, Han Wook" uniqKey="Yoo H" first="Han-Wook" last="Yoo">Han-Wook Yoo</name><affiliation><nlm:aff id="A1">Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</nlm:aff></affiliation></author></analytic><series><title level="j">Annals of Pediatric Endocrinology & Metabolism</title><idno type="ISSN">2287-1012</idno><idno type="eISSN">2287-1292</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Turner syndrome is one of the most common chromosomal disorders. It is caused by numerical or structural abnormalities of the X chromosome and results in short stature and gonadal dysgenesis. The short stature arises from haploinsufficiency of the <italic>SHOX</italic> gene, whereas overdosage contributes to tall stature. This report describes the first Korean case of Turner syndrome with tall stature caused by <italic>SHOX</italic> overdosage. The patient presented with primary amenorrhea and hypergonadotropic hypogonadism at the age of 17 years. Estrogen replacement therapy was initiated at that time. She displayed tall stature from childhood, with normal growth velocity, and reached a final height of 190 cm (standard deviation score, 4.3) at the age of 30 years. Her karyotype was 46,X, psu idic(X)(q21.2), representing partial monosomy of Xq and partial trisomy of Xp. Analysis by multiplex ligation-dependent probe amplification detected a duplication at Xp22.3-Xp22.2, encompassing the <italic>PPP2R3</italic> gene near the 5'-end of the <italic>SHOX</italic> gene through the <italic>FANCD</italic> gene at Xp22.2.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Stochholm, K" uniqKey="Stochholm K">K Stochholm</name></author><author><name sortKey="Juul, S" uniqKey="Juul S">S Juul</name></author><author><name sortKey="Juel, K" uniqKey="Juel K">K Juel</name></author><author><name sortKey="Naeraa, Rw" uniqKey="Naeraa R">RW Naeraa</name></author><author><name sortKey="Gravholt, Ch" uniqKey="Gravholt C">CH Gravholt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sybert, Vp" uniqKey="Sybert V">VP Sybert</name></author><author><name sortKey="Mccauley, E" uniqKey="Mccauley E">E McCauley</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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Ogata</name></author><author><name sortKey="Inokuchi, M" uniqKey="Inokuchi M">M Inokuchi</name></author><author><name sortKey="Ogawa, M" uniqKey="Ogawa M">M Ogawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nishi, My" uniqKey="Nishi M">MY Nishi</name></author><author><name sortKey="Correa, Rv" uniqKey="Correa R">RV Correa</name></author><author><name sortKey="Costa, Em" uniqKey="Costa E">EM Costa</name></author><author><name sortKey="Billerbeck, Ae" uniqKey="Billerbeck A">AE Billerbeck</name></author><author><name sortKey="Cruzes, Al" uniqKey="Cruzes A">AL Cruzes</name></author><author><name sortKey="Domenice, S" uniqKey="Domenice S">S Domenice</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kosho, T" uniqKey="Kosho T">T Kosho</name></author><author><name sortKey="Muroya, K" uniqKey="Muroya K">K Muroya</name></author><author><name sortKey="Nagai, T" uniqKey="Nagai T">T Nagai</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Ann Pediatr Endocrinol Metab</journal-id><journal-id journal-id-type="iso-abbrev">Ann Pediatr Endocrinol Metab</journal-id><journal-id journal-id-type="publisher-id">APEM</journal-id><journal-title-group><journal-title>Annals of Pediatric Endocrinology & Metabolism</journal-title></journal-title-group><issn pub-type="ppub">2287-1012</issn><issn pub-type="epub">2287-1292</issn><publisher><publisher-name>The Korean Society of Pediatric Endocrinology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26191517</article-id><article-id pub-id-type="pmc">4504991</article-id><article-id pub-id-type="doi">10.6065/apem.2015.20.2.110</article-id><article-categories><subj-group subj-group-type="heading"><subject>Case Report</subject></subj-group></article-categories><title-group><article-title>Turner syndrome presented with tall stature due to overdosage of the <italic>SHOX</italic> gene</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Seo</surname><given-names>Go Hun</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kang</surname><given-names>Eungu</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cho</surname><given-names>Ja Hyang</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Beom Hee</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Choi</surname><given-names>Jin-Ho</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Gu-Hwan</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Seo</surname><given-names>Eul-Ju</given-names></name><degrees>MD</degrees><degrees>PhD</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Yoo</surname><given-names>Han-Wook</given-names></name><degrees>MD</degrees><degrees>PhD</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</aff><aff id="A2"><label>2</label>Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.</aff><author-notes><corresp>Address for correspondence: Han-Wook Yoo, MD, PhD. Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3374, Fax: +82-2-473-3725, <email>hwyoo@amc.seoul.kr</email></corresp></author-notes><pub-date pub-type="ppub"><month>6</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>30</day><month>6</month><year>2015</year></pub-date><volume>20</volume><issue>2</issue><fpage>110</fpage><lpage>113</lpage><history><date date-type="received"><day>02</day><month>6</month><year>2015</year></date><date date-type="rev-recd"><day>15</day><month>6</month><year>2015</year></date><date date-type="accepted"><day>20</day><month>6</month><year>2015</year></date></history><permissions><copyright-statement>© 2015 Annals of Pediatric Endocrinology & Metabolism</copyright-statement><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Turner syndrome is one of the most common chromosomal disorders. It is caused by numerical or structural abnormalities of the X chromosome and results in short stature and gonadal dysgenesis. The short stature arises from haploinsufficiency of the <italic>SHOX</italic> gene, whereas overdosage contributes to tall stature. This report describes the first Korean case of Turner syndrome with tall stature caused by <italic>SHOX</italic> overdosage. The patient presented with primary amenorrhea and hypergonadotropic hypogonadism at the age of 17 years. Estrogen replacement therapy was initiated at that time. She displayed tall stature from childhood, with normal growth velocity, and reached a final height of 190 cm (standard deviation score, 4.3) at the age of 30 years. Her karyotype was 46,X, psu idic(X)(q21.2), representing partial monosomy of Xq and partial trisomy of Xp. Analysis by multiplex ligation-dependent probe amplification detected a duplication at Xp22.3-Xp22.2, encompassing the <italic>PPP2R3</italic> gene near the 5'-end of the <italic>SHOX</italic> gene through the <italic>FANCD</italic> gene at Xp22.2.</p></abstract><kwd-group><kwd>Turner syndrome</kwd><kwd>SHOX protein</kwd><kwd>Gonadal dysgenesis</kwd></kwd-group><funding-group><award-group><funding-source country="KR">National Research Foundation of Korea</funding-source><award-id>NRF-2011-0019674</award-id></award-group></funding-group></article-meta></front><body><sec sec-type="intro"><title>Introduction</title><p>Turner syndrome (TS) is one of the most common chromosomal disorders. It is caused by the loss of an X chromosome or the presence of a structurally abnormal X chromosome and has an estimated incidence of one in 2,500 girls born live<xref rid="B1" ref-type="bibr">1)</xref>. The cardinal features, which occur in more than 90% of TS cases, are short stature and gonadal dysgenesis<xref rid="B2" ref-type="bibr">2)</xref>. The patients with TS also have multisystemic complications such as congenital heart defects, skeletal anomalies, hearing impairment, ophthalmologic abnormalities, and renal structural anomalies<xref rid="B2" ref-type="bibr">2)</xref>. In addition, TS patients manifest dysmorphic features such as high arched palate, micrognathia, low-set ears, epicanthal folds, lymphedema of hands and feet, and webbed neck<xref rid="B2" ref-type="bibr">2)</xref>.</p><p>One candidate gene for short stature is located at the pseudoautosomal region 1 (PAR1) in the short arm of the X chromosome<xref rid="B3" ref-type="bibr">3)</xref>. This gene was discovered on the distal part of PAR1, and was designated the short stature homeobox-containing (<italic>SHOX</italic>) gene or pseudoautosomal homeobox-containing osteogenic (<italic>PHOG</italic>) gene<xref rid="B4" ref-type="bibr">4</xref><xref rid="B5" ref-type="bibr">5)</xref>. The <italic>SHOX</italic> gene is expressed in limbs, pharyngeal arches, osteogenic cells, and bone marrow fibroblasts, and is involved in skeletal growth and development<xref rid="B6" ref-type="bibr">6</xref><xref rid="B7" ref-type="bibr">7)</xref>. The loss of the <italic>SHOX</italic> gene therefore leads to short stature and various skeletal abnormalities, such as short metacarpals, high-arched palate, cubitus valgus, Madelung deformity, and mesomelia<xref rid="B6" ref-type="bibr">6</xref><xref rid="B7" ref-type="bibr">7)</xref>. The <italic>SHOX</italic> gene is expressed on both the inactive X chromosome and the active X or Y chromosome, thereby escaping from X chromosome inactivation<xref rid="B4" ref-type="bibr">4)</xref>. According to the altered <italic>SHOX</italic> dosage, haploinsufficiency causes short stature, while overdosage contributes to tall stature.</p><p>Several TS patients with tall stature caused by <italic>SHOX</italic> overdosage have been reported worldwide<xref rid="B8" ref-type="bibr">8</xref><xref rid="B9" ref-type="bibr">9</xref><xref rid="B10" ref-type="bibr">10</xref><xref rid="B11" ref-type="bibr">11)</xref>. Recently, we experienced the first Korean patient with tall stature caused by <italic>SHOX</italic> overdosage.</p></sec><sec><title>Case report</title><p>The patient was born at term, without any perinatal problems, to nonconsanguineous Korean parents. Her prenatal evaluation was unremarkable. She did not experience any particular problem until her late teens.</p><p>At 17 years of age, she was brought to medical attention because of primary amenorrhea and the absence of secondary sexual characteristics. She was 183.5 cm (standard deviation score [SDS], 3.3) tall and weighed 77.4 kg (SDS, 2.0). Her body mass index (BMI) was 23 kg/m<sup>2</sup> (SDS, 0.7). Her midparental height was 168.5 cm. Her serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were 19.9 mIU/mL and 32.5 mIU/mL, respectively. Her serum estradiol was <10 pg/mL. Transrectal ultrasonography (US) showed a normal-sized uterus and adnexa. Her abdominal US and echocardiogram were normal. Hormone replacement therapy was initiated with 0.625 mg of conjugated estrogen on day 1-23 and 10 mg of medroxyprogesterone acetate on day10-23 every month. There was no menstruation after 6 months of medication, and the medications were replaced with 2.06 mg of estradiol hemihydrate for 14 days and the addition of dydrogesterone (10 mg) for the next 14 days every month. At 18 years of age, the follow-up transrectal US showed no specific findings. She manifested pubertal development (breast and pubic hair, Tanner stage 3). However, she still did not menstruate.</p><p>She was referred to a pediatric endocrinology clinic at the age of 29 years during hormone replacement therapy. She was 190 cm (SDS, 4.3) tall and weighed 101 kg (SDS, 3.3), with a BMI of 28.1 kg/m<sup>2</sup> (SDS, 1.6). Her serum LH, FSH, and estradiol levels were 9.0 mIU/mL, 17.4 mIU/mL, and 18.1 pg/mL, respectively. Her serum triglyceride, total cholesterol, and high-density lipoprotein-cholesterol levels were 234 mg/dL, 138 mg/dL, and 34 mg/dL, respectively. Her blood pressure was normal. An x-ray of her left hand demonstrated complete epiphyseal fusion of the radius and ulna. Karyotype analysis revealed a nonmosaic pseudoisodicentric Xp chromosome, i.e., 46,X, psu idic(X)(q21.2) (<xref ref-type="fig" rid="F1">Fig. 1</xref>). Multiplex ligation-dependent probe amplification (MLPA) analysis identified duplication of the Xp22.3-Xp22.2 region, encompassing the <italic>SHOX</italic> gene (<xref ref-type="fig" rid="F2">Fig. 2</xref>).</p><p>She did not menstruate until she was 30 years old and still presented with breast and pubic hair at Tanner stage 3. Her weight had increased to 102.5 kg (SDS, 3.4) with a BMI of 28.4 kg/m2 (SDS, 1.7).</p></sec><sec sec-type="discussion"><title>Discussion</title><p>This report describes the first Korean case of a TS patient who presented with tall stature due to <italic>SHOX</italic> overdosage. Approximately 45% of patients with TS have a 45, X karyotype, 10% have an isochromosome Xq, and the remaining patients have mosaicism or structural abnormalities of the X chromosome<xref rid="B1" ref-type="bibr">1)</xref>. The present case had a nonmosaic 46, X, psu idic(Xq21.2) and presented with tall stature, surpassing the midparental height without other typical features of TS, except gonadal dysgenesis. The isochromosome X has a breakpoint at Xq21.2 and shows partial monosomy of Xq and partial trisomy of Xp. This implies a duplication of the terminal portion of Xp, including the <italic>SHOX</italic> gene. MLPA analysis confirmed the duplication from the <italic>PPP2R3</italic> gene at the Xp22.3 to the <italic>FANCD</italic> gene at the Xp22.2 region (<xref ref-type="fig" rid="F2">Fig. 2</xref>).</p><p>Several studies have demonstrated a correlation between <italic>SHOX</italic> overdosage and tall stature, as well as hypergonadotropic hypogonadism<xref rid="B9" ref-type="bibr">9</xref><xref rid="B10" ref-type="bibr">10)</xref>. <italic>SHOX</italic> overdosage and gonadal dysgenesis contribute to sustained growth, with constant height velocity from infancy to adolescence<xref rid="B9" ref-type="bibr">9</xref><xref rid="B10" ref-type="bibr">10)</xref>. The <italic>SHOX</italic> gene accelerates linear growth and inhibits fusion of the epiphyseal plate<xref rid="B12" ref-type="bibr">12</xref><xref rid="B13" ref-type="bibr">13)</xref>, resulting in a marked increase in leg length and subsequent change in body proportion<xref rid="B10" ref-type="bibr">10)</xref>. Although data are limited regarding the body ratio of the present case, a much longer lower than upper segment might be expected.</p><p>This patient continued to grow after 18 years of age, despite estrogen replacement therapy lasting 10 years, suggesting that <italic>SHOX</italic> overdosage surpasses the skeletal maturing effect of estrogen<xref rid="B9" ref-type="bibr">9)</xref>. However, other deleted genes on Xq or duplicated genes on Xp could have contributed to the tall stature of our patient.</p><p>A TS patient with mosaicism that includes a 45, X cell lineage can show a normal height until the early teens and can be taller than the target height until the late teens. This finding suggests that cell lineages determining height may be 46,X,idic(X) or 46,X,der(X), rather than the 45,X cell lineage<xref rid="B9" ref-type="bibr">9</xref><xref rid="B10" ref-type="bibr">10</xref><xref rid="B11" ref-type="bibr">11)</xref>. With this in mind, the present case showed tall stature until her late teens.</p><p>In summary, this report describes a TS patient with tall stature caused by a <italic>SHOX</italic> gene overdosage and estrogen deficiency, although tall stature could rarely be associated with TS in case of structurally abnormal X chromosome containing an extra Xp.</p></sec></body><back><ack><title>Acknowledgments</title><p>This study was supported by a grant from the National Research Foundation of Korea, funded by the Ministry of Education, Science, and Technology (NRF-2011-0019674).</p></ack><fn-group><fn fn-type="conflict"><p><bold>Conflict of interest:</bold> No potential conflict of interest relevant to this article was reported.</p></fn></fn-group><ref-list><ref id="B1"><label>1</label><element-citation publication-type="journal"><person-group 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person-group-type="author"><name><surname>Ogata</surname><given-names>T</given-names></name><name><surname>Matsuo</surname><given-names>N</given-names></name><name><surname>Nishimura</surname><given-names>G</given-names></name></person-group><article-title>SHOX haploinsufficiency and overdosage: impact of gonadal function status</article-title><source>J Med Genet</source><year>2001</year><volume>38</volume><fpage>1</fpage><lpage>6</lpage><pub-id pub-id-type="pmid">11134233</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="F1" orientation="portrait" position="float"><label>Fig. 1</label><caption><title>Chromosome analysis revealed 46,X, psu idic(Xq21.2). The arrow indicates a breakpoint at Xq21.2, indicating the deletion of the Xq21.2-Xqter and duplication of the Xpter-Xq21.2.</title></caption><graphic xlink:href="apem-20-110-g001"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Fig. 2</label><caption><title>Multiple ligation-dependent probe amplification (MLPA) analysis was performed using a SALSA MLPA P018-D1 Reference Kit (MRC Holland, Amsterdam, the Netherlands) according to the manufacturer's instructions. Amplified products were separated by electrophoresis and analyzed using an ABI3130 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA). The peak height of each probe was analyzed using Gene Mapper Software (Applied Biosystems). Duplication was detected at the Xp22.3-Xp22.2 region, including the <italic>SHOX</italic> gene.</title></caption><graphic xlink:href="apem-20-110-g002"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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