2004 Fiscal Year Final Research Report Summary
Clarification of genetic mechanisms leading to the whole phenotype in Turner syndrome
| Project/Area Number |
15591150
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
OGATA Tsutomu National Research Institute for Child Health and Development, Director, 部長 (40169173)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Naoko National Research Institute for Child Health and Development, Research Fellow, 研究員 (10383069)
FUKAMI MAKI National Research Institute for Child Health and Development, Research Fellow, 研究員 (40265872)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Turner syndrome / Sex choromosome / SHOX / Haploinsufficiency / Enhancer sequence / Gonadal function / Lymphogenic gene / Genotype-phenotype correlation |
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| Research Abstract |
The main results obtained in the research period is two-folds.
<Identification of the enhancer region for the SHOX expression>
We have previously studied more than 40 patienst with Leri-Weill syndrome, and identified SHOX deletion or mutation in 33 patients. In this research period, we found microdeltions at the 3' region of the SHOX gene in four patients with no demonstrable SHOX mutation. The smallest overlapping deleted region was determined as 39 kb, and in silico analysis disclosed 6 evolutionally conserved sequences within the 39 kb critical region. Thus, we performed luciferase assay with the evolutionally conserved sequences, and identified that a roughly 800 bp sequence has the transactivation function for the SHOX expression. The results suggest for the first time that the enhancer sequence for SHOX is present in the 800 bp region, and support the presence of an enhancer disorder. Furthermore, the identification of the molecule regulating the enhancer will permit to clarify the molecular network underlying the SHOX deficiency disorders.
<Localization of a lymphogenic gene>
We have previously proposed that the characteristic soft tissue and visceral features in Turner syndrome is explained as the malformation sequence initiated by lymphatic hypoplasia, suggesting the presence of an Xp-Yp homologous lymphogenic gene. In this research period, we performed genotype-phenotype correlation in 47 patients with partial Xp deletions and in 18 patients with partial Yp deletions, and localized the putative lymphogenic gene to a roughly 9 Mb region between MAOA and DMD on Xp and to an approximatedly 4 Mb region between PABY and DYS255 on Yp. Furthermore, we have identified three ESTs that may be regarded as the candidates for the lymphogenic gene,.
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Research Products
(19 results)
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[Journal Article] Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients.2005
Author(s)
Fukami, M., Horikawa, R., Nagai, T., Tanaka, T., Naiki, Y., Sato, N., Okuyama, T., Nakai, H., Soneda, S., Tachibana, K., Matsuo, N., Sato, S., Homma, K., Nishimura, G., Hasegawa, T., Ogata, T.
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Journal Title
Journal of Clinical Endocrinology and Metabolism 90
Pages: 414-426
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Statural growth in 31 Japanese patients with SHOX haploinsufficiency: support for a disadvantageous effect of gonadal estrogens.2004
Author(s)
Fukami, M., Nishi, Y., Hasegawa, Y., Miyoshi, Y., Okabe, T., Haga, N., Nagai, T., Tanaka, T., Ogata, T.
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Journal Title
Endocrine Journal 51(2)
Pages: 197-200
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Premature ovarian failure in a female with proximal symphalangism and NOG mutation.2004
Author(s)
Kosaki, K., Sato, S., Hasegawa, T., Matsuo, N., Suzuki, T., Ogata, T.
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Journal Title
Fertility and Sterility 81(4)
Pages: 1137-1139
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Protein tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome.2004
Author(s)
Yoshida, R., Hasegawa, T., Hasegawa, Y., Nagai, T., Kinoshita, E., Tanaka, Y., Kanegane, H., Ohyama, K., Onishi, T., Hanew, K., Okuyama, T., Horikawa, R., Tanaka, T., Ogata, T.
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Journal Title
Journal of Clinical Endocrinology and Metabolism 89(7)
Pages: 3359-3364
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Two novel and one recurrent PTPN11 mutations in LEOPARD syndrome.2004
Author(s)
Yoshida, R., Nagai, T., Hasegawa, T., Kinoshita, E., Tanaka, T., Ogata, T.
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Journal Title
American Journal of Medical Genetics 130A(4)
Pages: 432-434
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mental retardation in a boy with congenital adrenal hypoplasia: a clue to contiguous gene syndrome involving DAX-1 and IL1RAPL.2003
Author(s)
Sasaki, R., Inamo, Y., Saitoh, M., Hasegawa, T., Kinoshita, E., Ogata, T.
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Journal Title
Endocrine Journal 50(3)
Pages: 303-307
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Langer mesomelic dysplasia in a 45,X/46,X, r(X) infant with loss of SHOX from the ring X Chromosome and a microdeletion in the SHOX 3' region of the cytogenetically normal X chromosome.
Author(s)
Fukami, M., Okuyama, T., Yamamori, S., Nishimura, G., Ogata, T.
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Journal Title
American Journal of Medical Genetics. (in press)
Description
「研究成果報告書概要(欧文)」より
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