PDF(Sci-hub)
Abstract：
Albinism encompasses a group of hereditary disorders characterized by reduced or absent ocular pigment and variable skin and/or hair involvement, with syndromic forms such as Hermansky-Pudlak syndrome and Chédiak-Higashi syndrome. Autosomal recessive oculocutaneous albinism (OCA) is phenotypically and genetically heterogenous (associated with seven genes). X-linked ocular albinism (OA) is associated with only one gene, GPR143. We report the clinical and genetic outcomes of 44 patients, from 40 unrelated families of diverse ethnicities, with query albinism presenting to the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between November 2017 and October 2019. Thirty-six were children (≤ 16 years) with a median age of 31 months (range 2-186), and eight adults with a median age of 33 years (range 17-39); 52.3% (n = 23) were male. Genetic testing using whole genome sequencing (WGS, n = 9) or a targeted gene panel (n = 31) gave an overall diagnostic rate of 42.5% (44.4% (4/9) with WGS and 41.9% (13/31) with panel testing). Seventeen families had confirmed mutations in TYR (n = 9), OCA2, (n = 4), HPS1 (n = 1), HPS3 (n = 1), HPS6 (n = 1), and GPR143 (n = 1). Molecular diagnosis of albinism remains challenging due to factors such as missing heritability. Differential diagnoses must include SLC38A8-associated foveal hypoplasia and syndromic forms of albinism.
摘要：
白化病包括一组遗传性疾病，其特征是眼部色素减少或不存在，皮肤和/或头发受累可变，具有诸如Hermansky-Pudlak综合征和Chédiak-Higashi综合征等综合征形式。常染色体隐性遗传性眼皮肤白化病（OCA）在表型和遗传上具有异质性（与七个基因相关）。X连锁眼白化病（OA）仅与一个基因有关，GPR143。我们报告了44例患者的临床和遗传结果，来自40个不同种族的不相关家庭，在2017年11月至2019年10月期间，向Moorfields眼科医院NHS基金会信托基金的眼遗传学服务机构提出了白化病的查询。36为儿童（≤16岁），中位年龄为31个月（范围2-186），8名成年人，中位年龄为33岁（17-39岁）；52.3%（n=23）为男性。使用全基因组测序的基因检测(WGS，n=9）或靶向基因组（n=31）的总体诊断率为42.5％（WGS为44.4％（4/9），而小组测试为41.9％（13/31））。17个家族已确认TYR突变（n=9），OCA2,(n=4),HPS1（n=1），HPS3（n=1），HPS6(n=1),和GPR143(n=1)。由于遗传度缺失等因素，白化病的分子诊断仍然具有挑战性。鉴别诊断必须包括SLC38A8相关的中央凹发育不全和白化病的综合征形式。
