BACKGROUND Alström syndrome (AS) is a rare monogenic disorder characterized by progressive multi-organ pathology including retinal degeneration, hearing impairment and type 2 diabetes. Here we present clinical features in two siblings diagnosed with Alström syndrome associated with two novel changes in ALMS1. CASE PRESENTATION Two siblings originally diagnosed as having achromatopsia presented with mild light sensitivity, nonspecific otitis media, and mild developmental delay during the first decade of life with a relatively stable ocular appearance during second decade, late onset of nystagmus and dyschromatopsia (after 20 years) and preserved vision during the third decade of life. One sibling had late onset hearing loss and both siblings had symmetric high myopia, normal stature, and ptosis. Clinical findings revealed structural and functional tests consistent with a cone-rod dystrophy. Novel variants c.9894dupC (p.S3298 fs) and c.10769delC (p.T3590 fs) in ALMS1 gene were found. CONCLUSIONS Two North American siblings who presented with a mild clinical phenotype of Alström syndrome were found to have novel mutations in ALMS1. These two frame-shift mutations segregated with the disease phenotype lending evidence to their pathogenicity.

中文翻译：

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与两个新的ALMS1变体相关的两个Alstrom综合征同胞且没有听力损失的病例报告。

背景技术Alström综合征（AS）是一种罕见的单基因疾病，其特征是进行性多器官病变包括视网膜变性，听力障碍和2型糖尿病。在这里，我们介绍两个被诊断为Alström综合征且与ALMS1的新变化有关的兄弟姐妹的临床特征。病例介绍最初被诊断为患有色盲的两个兄弟姐妹，在生命的第一个十年中表现出轻度的光敏感性，非特异性中耳炎和轻度的发育迟缓，在第二个十年中具有相对稳定的眼部外观，眼球震颤和迟发性色盲（20年后）并在生命的第三个十年中保留了远见。一位兄弟姐妹患有迟发性听力丧失，并且两个兄弟姐妹均患有对称性高度近视，身材正常和上睑下垂。临床发现显示与锥体营养不良相符的结构和功能测试。在ALMS1基因中发现了新的变体c.9894dupC（p.S3298 fs）和c.10769delC（p.T3590 fs）。结论两名患有Alström综合征临床表型较轻的北美兄弟姐妹在ALMS1中发现了新的突变。这两个移码突变与疾病表型分开，为它们的致病性提供了证据。