Novel homozygous, heterozygous and hemizygous FRMD7 gene mutations segregated in the same consanguineous family with congenital X-linked nystagmus
Novel homozygous, heterozygous and hemizygous FRMD7 gene mutations segregated in the same consanguineous family with congenital X-linked nystagmus
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DOI：
10.1038/ejhg.2012.60
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发表时间：
2012-10-01
影响因子：
5.2
通讯作者：
Antonarakis, Stylianos E.
中科院分区：
文献类型：
--
作者：
Radhakrishna, Uppala;Ratnamala, Uppala;Antonarakis, Stylianos E.
先天性眼球震颤(NYS)的特征是双眼、自发和不自主的眼球运动，最常见的表现为2至6个月的生命。到目前为止，已发现44种不同的FRMD7基因突变是NYS1基因Xq26-Q27的致病因素。这项研究的目的是在一个有71名成员受到NYS影响的印度11代大家系中发现FRMD7基因突变。对FRMD7基因整个编码区和剪接接头的突变分析显示，一个新的错义突变c.A917G预测了FRMD7基因外显子10中密码子305(Q305R)上的Arg取代Gln。在半合子男性中检测到突变，在受影响的女性家庭成员中检测到纯合子和杂合子状态。在该家族中未受影响的成员或100名无血缘关系的对照受试者中未发现该突变。在受影响的家族成员中，该突变被发现位于FERM相邻结构域中的高度保守的残基上。与突变体(Q305R)相比，野生型FRMD7的结构预测和能量分析表明，氨基酸的这种变化导致了二级结构的变化，预测这是一种能量不稳定的蛋白质。这项研究首次证实了一个多代印度家庭的FRMD7基因突变，并扩大了该基因座的突变谱。《欧洲人类遗传学杂志》(2012年)201032年至1036年；DOI：10.1038/ejhg.2012.60；2012年4月11日在线发布
Congenital nystagmus (NYS) is characterized by bilateral, spontaneous, and involuntary movements of the eyeballs that most commonly presents between 2 and 6 months of life. To date, 44 different FRMD7 gene mutations have been found to be etiological factors for the NYS1 locus at Xq26-q27. The aim of this study was to find the FRMD7 gene mutations in a large eleven-generation Indian pedigree with 71 members who are affected by NYS. Mutation analysis of the entire coding region and splice junctions of the FRMD7 gene revealed a novel missense mutation, c.A917G, predicts a substitution of Arg for Gln at codon 305 (Q305R) within exon 10 of FRMD7. The mutation was detected in hemizygous males, and in homozygous and heterozygous states in affected female members of the family. This mutation was not detected in unaffected members of the family or in 100 unrelated control subjects. This mutation was found to be at a highly conserved residue within the FERM-adjacent domain in affected members of the family. Structure prediction and energetic analysis of wild-type FRMD7 compared with mutant (Q305R) revealed that this change in amino acid led to a change in secondary structure predicted to be an energetically unstable protein. The present study represents the first confirmation of FRMD7 gene mutations in a multigenerational Indian family and expands the mutation spectrum for this locus. European Journal of Human Genetics (2012) 20, 1032-1036; doi: 10.1038/ejhg.2012.60; published online 11 April 2012