Self James E, Shawkat Fatima, Malpas Crispin T, Thomas N Simon, Harris Christopher M, Hodgkins Peter R, Chen Xiaoli, Trump Dorothy, Lotery Andrew J
Clinical Neurosciences Division, University of Southampton, Southampton, England.
Arch Ophthalmol. 2007 Sep;125(9):1255-63. doi: 10.1001/archopht.125.9.1255.
To perform a genotype-phenotype correlation study in an X-linked congenital idiopathic nystagmus pedigree (pedigree 1) and to assess the allelic variance of the FRMD7 gene in congenital idiopathic nystagmus.
Subjects from pedigree 1 underwent detailed clinical examination including nystagmology. Screening of FRMD7 was undertaken in pedigree 1 and in 37 other congenital idiopathic nystagmus probands and controls. Direct sequencing confirmed sequence changes. X-inactivation studies were performed in pedigree 1.
The nystagmus phenotype was extremely variable in pedigree 1. We identified 2 FRMD7 mutations. However, 80% of X-linked families and 96% of simplex cases showed no mutations. X-inactivation studies demonstrated no clear causal link between skewing and variable penetrance.
We confirm profound phenotypic variation in X-linked congenital idiopathic nystagmus pedigrees. We demonstrate that other congenital nystagmus genes exist besides FRMD7. We show that the role of X inactivation in variable penetrance is unclear in congenital idiopathic nystagmus. Clinical Relevance We demonstrate that phenotypic variation of nystagmus occurs in families with FRMD7 mutations. While FRMD7 mutations may be found in some cases of X-linked congenital idiopathic nystagmus, the diagnostic yield is low. X-inactivation assays are unhelpful as a test for carrier status for this disease.
在一个X连锁先天性特发性眼球震颤家系（家系1）中进行基因型-表型相关性研究，并评估先天性特发性眼球震颤中FRMD7基因的等位基因变异情况。
家系1中的受试者接受了包括眼球震颤学在内的详细临床检查。对家系1以及另外37名先天性特发性眼球震颤先证者和对照进行了FRMD7筛查。直接测序确定了序列变化。在家系1中进行了X染色体失活研究。
家系1中的眼球震颤表型极具变异性。我们鉴定出2个FRMD7突变。然而，80%的X连锁家系和96%的散发病例未显示出突变。X染色体失活研究表明，偏态与可变外显率之间没有明确的因果联系。
我们证实了X连锁先天性特发性眼球震颤家系中存在显著的表型变异。我们证明除了FRMD7之外，还存在其他先天性眼球震颤基因。我们表明，X染色体失活在先天性特发性眼球震颤可变外显率中的作用尚不清楚。临床意义我们证明了FRMD7突变家系中存在眼球震颤的表型变异。虽然在某些X连锁先天性特发性眼球震颤病例中可能发现FRMD7突变，但诊断率较低。X染色体失活检测对该病携带者状态的检测并无帮助。
