Francis P J, Johnson S, Edmunds B, Kelsell R E, Sheridan E, Garrett C, Holder G E, Hunt D M, Moore A T
Institute of Ophthalmology, University College London, 11-43 Bath Street, London, UK.
Br J Ophthalmol. 2003 Jul;87(7):893-8. doi: 10.1136/bjo.87.7.893.
To characterise the phenotype and identify the underlying genetic defect in a family with deafness segregating with a North Carolina-like macular dystrophy (NCMD).
Details of the family were obtained from the Moorfields Eye Hospital genetic clinic database and comprised eight affected, four unaffected members, and two spouses. Pedigree data were collated and leucocyte DNA extracted from venous blood. Positional candidate gene and genetic linkage strategies utilising polymerase chain reaction (PCR) based microsatellite marker genotyping were performed to identify the disease locus.
The non-progressive ocular phenotype shared similarities with North Carolina macular dystrophy. Electro-oculography and full field electroretinography were normal. Progressive sensorineural deafness was also present in all affected individuals over the age of 20 years. Hearing was normal in all unaffected relatives. Haplotype analysis indicated that this family is unrelated to previously reported families with NCMD. Genotyping excluded linkage to the MCDR1 locus and suggested a potential novel disease locus on chromosome 14q (Z=2.92 at theta=0 for marker D14S261).
The combination of anomalies segregating in this family represents a novel phenotype. This molecular analysis indicates the disease is genetically distinct from NCMD.
对一个伴有类似北卡罗来纳黄斑营养不良（NCMD）的耳聋家系的表型进行特征描述，并确定其潜在的基因缺陷。
从摩尔菲尔兹眼科医院遗传门诊数据库获取该家系的详细信息，包括八名患者、四名未患病成员和两名配偶。整理系谱数据，并从静脉血中提取白细胞DNA。利用基于聚合酶链反应（PCR）的微卫星标记基因分型进行定位候选基因和遗传连锁分析，以确定疾病位点。
非进行性眼部表型与北卡罗来纳黄斑营养不良相似。眼电图和全视野视网膜电图正常。所有20岁以上的患者均存在进行性感音神经性耳聋。所有未患病亲属听力正常。单倍型分析表明，该家系与先前报道的NCMD家系无关。基因分型排除了与MCDR1位点的连锁关系，并提示在14号染色体q区存在一个潜在的新疾病位点（标记D14S261在θ=0时Z=2.92）。
该家系中分离出的异常组合代表一种新的表型。这种分子分析表明该疾病在基因上与NCMD不同。
