Ksantini Mohamed, Lafont Estèle, Bocquet Béatrice, Meunier Isabelle, Hamel Christian P
INSERM 1051, Institute for Neurosciences of Montpellier, Montpellier, France.
Eur J Ophthalmol. 2012 Jul-Aug;22(4):647-53. doi: 10.5301/ejo.5000096.
Gene identification in retinitis pigmentosa is a prerequisite to future therapies. Accordingly, autosomal recessive retinitis pigmentosa families were genotyped to search for causative mutations.
Members of a consanguineous Moroccan family had standard ophthalmologic examination, optical coherence tomography-3 scan, autofluorescence testing, and electroretinogram. Their DNA was genotyped with the 250K SNP microchip (Affymetrix) and homozygosity mapping was done. MERTK exons were polymerase chain reaction amplified and sequenced.
Two sisters and one brother out of 6 siblings had rod cone dystrophy type of retinitis pigmentosa. Salient features were night blindness starting in early infancy, dot-like whitish deposits in fovea and macula with corresponding autofluorescent dots in youngest patients, decreased visual acuity, and cone responses higher than rod responses at electroretinogram. The patients were homozygous in regions from chromosomes 2 and 8, but only that of chromosome 2 was inherited from a common ancestor. Sequencing of the MERTK gene belonging to the chromosome 2 region showed that the 3 affected patients carried a novel homozygous mutation in exon 17, c.2323C>T, leading to p.Arg775X, while their unaffected brothers and sister, parents, and paternal grandfather were heterozygous.
MERTK mutations lead to severe retinitis pigmentosa with discrete dot-like autofluorescent deposits at early stages, which are a hallmark of this MERTK-specific dystrophy.
视网膜色素变性中的基因鉴定是未来治疗的前提条件。因此，对常染色体隐性视网膜色素变性家族进行基因分型以寻找致病突变。
一个近亲摩洛哥家族的成员接受了标准眼科检查、光学相干断层扫描-3扫描、自发荧光测试和视网膜电图检查。他们的DNA用250K SNP微芯片（Affymetrix）进行基因分型，并进行纯合性定位。MERTK外显子通过聚合酶链反应扩增并测序。
6名兄弟姐妹中有2名姐妹和1名兄弟患有视锥视杆营养不良型视网膜色素变性。显著特征包括婴儿早期开始出现夜盲症、中央凹和黄斑有斑点状白色沉积物，最年轻患者中有相应的自发荧光点、视力下降以及视网膜电图中视锥细胞反应高于视杆细胞反应。患者在2号和8号染色体区域是纯合子，但只有2号染色体区域是从共同祖先遗传而来。对属于2号染色体区域的MERTK基因进行测序显示，3名患病患者在第17外显子中携带一个新的纯合突变，c.2323C>T，导致p.Arg775X，而他们未患病的兄弟姐妹、父母和祖父是杂合子。
MERTK突变导致严重的视网膜色素变性，早期有离散的斑点状自发荧光沉积物，这是这种MERTK特异性营养不良的一个标志。
