Oki Ryoko, Yamada Kisaburo, Nakano Satoko, Kimoto Kenichi, Yamamoto Ken, Kondo Hiroyuki, Kubota Toshiaki
Department of Ophthalmology, Oita University Faculty of Medicine, Oita, Japan.
Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, Japan.
Invest Ophthalmol Vis Sci. 2017 Feb 1;58(2):1008-1016. doi: 10.1167/iovs.16-20612.
We report the clinical characteristics of a Japanese family with autosomal dominant oculocutaneous albinism and a SLC45A2 gene mutation.
A total of 16 members of a Japanese family with general hypopigmentation and foveal hypoplasia underwent detailed clinical examinations. We evaluated the severity of foveal hypoplasia using spectral-domain optical coherence tomography (SD-OCT) and graded it according to the criteria of Thomas et al. DNA was extracted from 17 family members and used for genome-wide single nucleotide polymorphism genotyping and linkage analysis. Mutational search was performed for the SLC45A2 gene responsible for oculocutaneous albinism type 4 (OCA4).
All 16 patients exhibited hypopigmentation of their hair and/or iris. They showed foveal hypoplasia, including 3 patients with grade 1 foveal hypoplasia, 7 with grade 2, and 6 with grade 3. No patient had grade 4 foveal hypoplasia. Optical coherence tomography showed macular ganglion cell complex thinning in the temporal area, and a slight reduction of visual field sensitivity in the centrotemporal area. A maximum multipoint parametric logarithm of the odds (LOD) score of approximately 2.00 to 3.56 was obtained on chromosome 5, spanning approximately 7.2 Mb between rs13187570 and rs395967 that included the SLC45A2 gene. All affected members showed a novel heterozygous variant, c.208T>C (p.Y70H), in the SLC45A2 gene, which supported a diagnosis of OCA4.
The present study reports a very rare family with autosomal dominant OCA4 whose diagnosis was confirmed by a mutational analysis. Most family members exhibited mild general hypopigmentation and low-grade foveal hypoplasia.
我们报告一个患有常染色体显性遗传性眼皮肤白化病及SLC45A2基因突变的日本家族的临床特征。
一个有全身色素减退和黄斑发育不全的日本家族的16名成员接受了详细的临床检查。我们使用光谱域光学相干断层扫描（SD-OCT）评估黄斑发育不全的严重程度，并根据托马斯等人的标准进行分级。从17名家族成员中提取DNA，用于全基因组单核苷酸多态性基因分型和连锁分析。对导致4型眼皮肤白化病（OCA4）的SLC45A2基因进行突变搜索。
所有16例患者均有头发和/或虹膜色素减退。他们表现出黄斑发育不全，其中3例为1级黄斑发育不全，7例为2级，6例为3级。无4级黄斑发育不全患者。光学相干断层扫描显示颞侧黄斑神经节细胞复合体变薄，中央颞侧区域视野敏感度略有降低。在5号染色体上获得了约2.00至3.56的最大多点参数优势对数（LOD）分数，跨越rs13187570和rs395967之间约7.2 Mb，其中包括SLC45A2基因。所有受影响成员在SLC45A2基因中均表现出一种新的杂合变异，即c.208T>C（p.Y70H），这支持了OCA4的诊断。
本研究报告了一个非常罕见的常染色体显性OCA4家族，其诊断通过突变分析得到证实。大多数家族成员表现为轻度全身色素减退和低度黄斑发育不全。
