A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1
A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1
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DOI：
10.1093/humrep/deq006
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发表时间：
2010-04-01
影响因子：
6.1
通讯作者：
Masuzaki, Hideaki
中科院分区：
文献类型：
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作者：
Miura, Kiyonori;Miura, Shoko;Masuzaki, Hideaki
成纤维细胞生长因子受体1（Fibroblast growth factor receptor 1，FGFR 1）是卡尔曼综合征（Kallmann syndrome，KS）的致病基因之一。FGFR 1的第三免疫球蛋白样结构域（D3）具有同种型FGFR 1-IIIb和FGFR 1-IIIc，其分别通过外显子8A和8B的选择性剪接产生。迄今为止，在FGFR 1的D3中鉴定的唯一突变是外显子8B。我们对一例23岁女性KS患者进行了FGFR 1基因突变分析，发现FGFR 1基因外显子8A存在错义突变（c.1072C > T）。在她的家庭成员或220名正常日本人和100名白人女性对照中未检测到c.1072C > T突变。在受影响的患者或其家庭成员中未检测到其他KS基因KS 1、前动力蛋白-2、前动力蛋白受体-2和FGF-8的突变。因此，这是第一例在FGFR 1外显子8A中携带从头错义突变的KS，表明亚型FGFR 1-IIIb以及亚型FGFR 1-IIIc在KS的发病机制中起着至关重要的作用。
Fibroblast growth factor receptor 1 (FGFR1) is one of the causative genes for Kallmann syndrome (KS), which is characterized by isolated hypogonadotropic hypogonadism with anosmia/hyposmia. The third immunoglobulin-like domain (D3) of FGFR1 has the isoforms FGFR1-IIIb and FGFR1-IIIc, which are generated by alternative splicing of exons 8A and 8B, respectively. To date, the only mutations to have been identified in D3 of FGFR1 are in exon 8B. We performed mutation analysis of FGFR1 in a 23-year-old female patient with KS and found a missense mutation (c.1072C > T) in exon 8A of FGFR1. The c.1072C > T mutation was not detected in her family members or in 220 normal Japanese and 100 Caucasian female controls. No mutation in other KS genes, KS 1, prokineticin-2, prokineticin receptor-2 and FGF-8 was detected in the affected patient or in her family members. Therefore, this is the first case of KS carrying a de novo missense mutation in FGFR1 exon 8A, suggesting that isoform FGFR1-IIIb, as well as isoform FGFR1-IIIc, plays a crucial role in the pathogenesis of KS.