Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2).
Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2).
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DOI：
10.1002/humu.9298
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发表时间：
2005-01-01
期刊：
影响因子：
3.9
通讯作者：
Dode, Catherine
中科院分区：
文献类型：
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作者：
Albuisson, Juliette;Pecheux, Chistophe;Dode, Catherine
Kallmann综合征(KAL)合并性腺激素减退和嗅觉障碍。性腺功能减退是由于促性腺激素释放激素(GnRH)缺乏所致，嗅觉障碍与嗅球发育不良有关。偶尔出现的症状包括肾发育不全、双手联动、唇腭裂、牙齿发育不全。KAL在遗传上是异质性的，目前已鉴定出两个基因，即KAL1(Xp22.3)和FGFR1/KAL2(8p12)，分别构成X染色体连锁形式和常染色体显性形式。我们研究了98名无关的高加索人KAL患者的队列。我们在14例患者中发现了KAL1突变，其中7例(c.3G和gt；A(p.M1？)，c.IVS1+1G>；T，c.570_571insA(p.R191fsX14)，c.784G>；C(p.R262P)，c.958G>；T(p.E320X)，c.1651_1654delinsAGCT(p.P551_E552delinsSX)，c.1711T>；A(p.W571R)。此外，我们在7例患者中发现了FGFR1突变，即c.303G>；A(p.V102I)、C.385A>；C(p.D129A)、c.810G>；A(p.V273M)、c.1093_1094delAG(p.R365fsX41)、c.1561G>；A(p.A520T)、c.1836_1837insT(p.Y613fsX42)、c.2190C>；G(p.Y730X)。在这项研究中，单侧肾发育不全和双臂联动完全与KAL1突变、腭裂和牙齿发育不全有关，FGFR1突变。
Kallmann syndrome (KAL) combines hypogonadotropic hypogonadism and anosmia. Hypogonadism is due to Gonadotropin Releasing Hormone (GnRH) deficiency and anosmia is related to hypoplasia of the olfactory bulbs. Occasional symptoms include renal agenesis, bimanual synkinesia, cleft lip palate, dental agenesis. KAL is genetically heterogeneous and two genes have so far been identified, namely KAL1 (Xp22.3) and FGFR1/KAL2 (8p12), which underlie the X chromosome-linked form and an autosomal dominant form of the disease, respectively. We studied a cohort of 98 unrelated Caucasian KAL patients. We identified KAL1 mutations in 14 patients, of which 7 (c.3G>A (p.M1?), g.IVS1+1G>T, c.570_571insA (p.R191fsX14), c.784G>C (p.R262P), c.958G>T (p.E320X), c.1651_1654delinsAGCT (p.P551_E552delinsSX), c.1711T>A (p.W571R)) have not been previously reported. In addition, we found FGFR1 mutations in 7 patients, namely c.303G>A (p.V102I), C.385A>C (p.D129A), c.810G>A (p.V273M), c.1093_1094delAG (p.R365fsX41), c.1561G>A (p.A520T), c.1836_1837insT (p.Y613fsX42), c.2190C>G (p.Y730X), all of which were novel mutations. In this study, unilateral renal agenesis and bimanual synkinesia were exclusively found associated with KAL1mutations, cleft palate and dental agenesia with FGFR1mutations.