London Eye Diagnostic Centre, London, UK.
Eye (Lond). 2010 Nov;24(11):1659-68. doi: 10.1038/eye.2010.103. Epub 2010 Aug 13.
To report a new phenotype with additional data on the oculo-dental syndrome of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) caused by mutations on CNNM4, a metal transporter, with linkage at achromatopsia locus 2q11 (Jalili syndrome).
Three siblings aged 5, 6, and 10 years from a six-generation Arab family in Gaza City underwent full systemic, ophthalmic, and dental examinations, investigations and detailed genealogy.
Subjects presented at early childhood with visual impairment and abnormal dentition together with photophobia and fine nystagmus increasing under photopic conditions, in the presence of normal fundi. Electrophysiologically, photopic flicker responses were impaired; scotopic responses were extinguished at the age of 10 years. Anterior open bite accompanied AI in all siblings. The syndrome formed 83% of CRD cases in the Gaza Strip, which has a prevalence of 1 : 10,000.
On the basis of clinical features and electrophysiology, two phenotypes exist: an infancy onset form with progressive macular lesion and an early childhood onset form with normal fundi. More prevalent than previously thought, Jalili syndrome presents a model of the effect of different mutations of the same genetic defect, observations of the same phenotype at different stages of the natural history of the disease, and the influence of epigenetic and tissue-specific factors as causes of phenotypic variability. The paper calls for action to tackle consanguinity in endogamous communities, addresses the possible role of high fluoride levels in groundwater as a trigger for genetic mutations, and the use of red-tinted filter in cone disorders.
报道一种新的表型，并提供更多关于 CNNM4 基因突变导致的 Cone-Rod 营养不良（CRD）和牙本质发育不全（AI）的眼-齿综合征的资料，该基因突变也与无色素性视网膜炎 2q11 （Jalili 综合征）位点相关。
来自加沙市一个六代阿拉伯家庭的 3 名 5、6 和 10 岁的兄弟姐妹接受了全面的系统、眼科和牙科检查、调查和详细的家族史研究。
受检者在幼儿期即出现视力障碍和牙齿异常，同时伴有畏光和在明适应条件下增加的细震颤，眼底正常。电生理检查显示，光闪烁反应受损；10 岁时，暗适应反应消失。所有兄弟姐妹均存在前牙开颌和牙本质发育不全。该综合征在加沙地带的 CRD 病例中占 83%，患病率为 1：10000。
根据临床特征和电生理学表现，存在两种表型：一种是进行性黄斑病变的婴儿期发病型，另一种是眼底正常的幼儿期发病型。与之前认为的相比，Jalili 综合征为同一遗传缺陷的不同突变所产生的影响、疾病自然史的不同阶段观察到的相同表型以及表观遗传和组织特异性因素作为表型变异性的原因提供了一个模型。该研究呼吁采取行动解决近亲婚姻问题，探讨地下水高氟水平作为基因突变的触发因素的可能性，以及在 Cone 障碍中使用红色滤光片的作用。
