Genetic analysis in patients with hypogonadotropic hypogonadism accompanied by dysosmia -Analysis of the KAL1 gene in patient with Kallmann syndrome-
| Project/Area Number |
13672420
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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 |
Laboratory medicine
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| Research Institution | Osaka University |
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Principal Investigator |
IZUMI Yukiko Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (60314316)
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| Co-Investigator(Kenkyū-buntansha) |
TATSUMI Keita Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (00222109)
OKAMOTO Shingo Nara Medical University, Third Department of Internal Medicine, Assistant Professor, 第3内科, 助教授 (10086572)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2004: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 2003: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 2002: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | Kallmann Syndrome / Hypogonadotropic Hypogonadism / Dysosmia / KAL1 gene / Hemirenal Hypoplasia / Mirror Movement / KAL1 protein |
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| Research Abstract |
Kallmann syndrome is defined by the association of hypogonadotropic hypogonadism and anosmia. The KAL1 gene is responsible for the X-linked form of Kallmann syndrome. We analyzed the KAL1 gene in 19 Japanese patients with Kallmann syndrome using PCR-direct sequencing method. All of 19 patients were sporadic, except for two male monozygotic twins. Seventeen patients were males and two were females. In this study, we found three kinds of novel mutations in the KAL1 gene. One of them existed in monozygotic twins.
The severity of hypogonadism was riot related to the presence of mutations or polymorphisms. Unilateral renal aplasia and mirror movement, which are frequently hand in patients with the KAL1 gene mutations, were not related to the sites of mutations.
In male sporadic patients with Kallmann syndrome, the incidence of mutations in Japanese patients (14% : 2 of 14 cases) was slightly higher than that in patients in USA (8%). But there was no significant difference between the two groups as shown by Fisher's exact test. Meanwhile we found two polymorphisms, such as Ile534Val and Ile611, which were always found together in 6 patients.
Mutations in the KAL1 gene previously reported were widely distributed from exon 1 to exon 13 and different among families except at two sites. In our study, one mutation was inherited from mother and another mutation derived from the patient. Therefore these mutations could not have been derived from common ancestor by a founder gene effect. We consider that mutation in the KAL1 gene is difficult to be inherited because of male infertility.
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Report
(5 results)
Research Products
(34 results)
