Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome
Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome
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DOI：
10.1038/ng1122
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发表时间：
2003-04-01
期刊：
影响因子：
30.8
通讯作者：
Hardelin, JP
中科院分区：
文献类型：
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作者：
Dodé, C;Levilliers, J;Hardelin, JP
我们利用重叠间质缺失染色体8 p11-p12在两个人连续的基因综合征和定义的间隔约540 kb与卡尔曼综合征，KAL 2的显性形式。我们在此证实，FGFR 1的功能缺失突变是KAL 2的基础，而FGFR 1的功能获得突变已被证明会导致一种形式的颅缝早闭。此外，我们认为KAL 1基因产物，细胞外基质蛋白anosmin-1，参与FGF信号传导，并提出anosmin-1剂量的性别差异（因为KAL 1部分逃避X失活）解释了男性疾病的患病率较高。
We took advantage of overlapping interstitial deletions at chromosome 8p11-p12 in two individuals with contiguous gene syndromes and defined an interval of roughly 540 kb associated with a dominant form of Kallmann syndrome, KAL2. We establish here that loss-of-function mutations in FGFR1 underlie KAL2 whereas a gain-of-function mutation in FGFR1 has been shown to cause a form of craniosynostosis. Moreover, we suggest that the KAL1 gene product, the extracellular matrix protein anosmin-1, is involved in FGF signaling and propose that the gender difference in anosmin-1 dosage (because KAL1 partially escapes X inactivation) explains the higher prevalence of the disease in males.