卡爾曼氏症候群病人個案的分子遺傳學研究

The study of Molecular Genetics of clients from patients with Kallmann Syndrome

楊麗巧(Li-Chiao Yang)

指導教授 ： 楊偉勛

國立臺灣大學/醫學院/分子醫學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.10639

摘要

卡爾曼氏症候群（Kallmann Syndrome）是X染色體及體染色體上基因缺陷所造成的遺傳疾病，主要是性腺激素功能低下與性腺功能低下伴隨嗅覺缺失或嗅覺低下。卡爾曼氏症候群屬於極為罕見的疾病，發生率約為1/8,000個出生男嬰與1/40,000個出生女嬰。目前已知卡爾曼氏症候群分成六個基因型：KAL1、KAL 2、KAL 3、KAL 4、KAL 5和KAL 6。其中KAL 1、KAL 2、KAL 3、KAL 4這四型在卡爾曼氏症候群中約佔30%。文獻報告指出，卡爾曼氏症候群患者可藉由早期臨床介入，如由賀爾蒙替代療法來改善病徵。
本研究中收集了一位女性、七位男性，共計八名疑似為卡爾曼氏症候群病人。我們利用聚合酶連鎖反應技術，試圖從中找出關於卡爾曼氏症候群第二型、第三型及第四型基因的突變點位。檢測結果發現個案均無第二型、第三型及第四型的突變點，而案例中的一名七歲男童之前已被證實KAL-1 geene發生突變。建議下位研究者可以選擇其他疾病候選基因或除了點突變以外的技術來進一步探索；甚至，精確的臨床診斷對卡爾曼氏症候群是一個重要的研究意義。

關鍵字

卡爾曼氏症候群 ； 下視丘－腦下垂腺軸 ； 促性腺激素分泌不足的低性腺功能症 ； 嗅覺喪失 ； 青春期遲緩

並列摘要

Kallmann Syndrome （KS）, an inherited syndrome with gene defects carried by the X chromosome and autosome chromosomes, characterized by hypogonadotropic hypogonadism with anosmia or hypoosmia. KS is a rare syndrome with an incidence of 1/8000 in male babies and 1/40000 in female babies. There are six KS genes identified：KAL-1, KAL-2, KAL-3, KAL-4, KAL-5 and KAL-6. The first four types, KAL-1, KAL-2, KAL-3 and KAL-4, almost take up 30% of KS cases. With the advancement in the KS research, the clinical manifestations of KS patients can be improved by early clinical interventions, such as the hormone replacement therapy（HRT）.
In this study, we collected samples from one female, and seven males who are suspected to have KS. One boy was previously identified to have mutation in KAL-1 gene. In this study, I screened mutation of KAL-2, KAL-3, and KAL-4 of KS from these samples by direct PCR-sequencing. We did not find any mutation among them. Further exploration of the other candidate genes or the use of the other genotyping technologies for mutations other than point mutation should be employed in the future. A precise clinical protocol for future genetic study is also important to improve the quality of this genetic study.

並列關鍵字

Kallmann Syndrome ； Hypothalamic-Pituitary Axis ； Hypogonadotropic ； Hypogonadism（HH） ； Anosmia ； Delayed Puberty

參考文獻

【3】財團法人罕見疾病基金會 http://www.tfrd.org.tw/

【1】吳哲宗:卡曼氏症候群患者（Kallmann Syndrome）在KAL-1 基因上突變的搜尋與探討—以台大醫院的病患為例.2009

【4】黃愛珠:『腎上腺腦白質退化症』的壓力因應.2006

【44】Madan R, Sawlani V, Gupta S, et al. MRI findings in Kallmann syndrome. Neurol India 2004; 52:501–503.

【14】Naoko Sato, Noriyuki Katsumata, Masayo Kagami, Tomonobu Hasegawa, Naoaki Hori, Setsuyo Kawakita, Shigeru Minowada, Aki Shimotsuka, Yoshimasa Shishiba, Masato Yokozawa, Toshiyuki Yasuda, Keisuke Nagasaki, Daiichiro Hasegawa, Yukihiro Hasegawa, Katsuhiko Tachibana, Yasuhiro Naiki, Reiko Horikawa, Toshiaki Tanaka and Tsutomu Ogata: Clinical Assessment and Mutation Analysis of Kallmann Syndrome 1 （KAL1） and Fibroblast Growth Factor Receptor 1 （FGFR1, or KAL2） in Five Families and 18 Sporadic Patients. The Journal of Clinical Endocrinology & Metabolism. 2004（89） 1079-1088.