Research group on Molecular, Cellular and Genomic Biomedicine, Health Research, Institute La Fe (IIS La Fe) and Mixed Unit for Rare diseases IIS La Fe - CIPF, Valencia, Spain.
Centre for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
Mol Vis. 2020 Mar 18;26:216-225. eCollection 2020.
The aim of the present work is the molecular diagnosis of three patients with deafness and retinal degeneration.
Three patients from two unrelated families were initially analyzed with custom gene panels for Usher genes, non-syndromic hearing loss, or inherited syndromic retinopathies and further investigated by means of clinical or whole exome sequencing.
The study allowed us to detect likely pathogenic variants in , a gene typically involved in peroxisomal biogenesis disorders (PBDs). Beside deaf-blindness, both families showed additional features: Siblings from Family 1 showed enamel alteration and abnormal peroxisome. In addition, the brother had mild neurodevelopmental delay and nephrolithiasis. The case II:1 from Family 2 showed intellectual disability, enamel alteration, and dysmorphism.
We have reported three new cases with pathogenic variants in presenting with milder forms of the Zellweger spectrum disorders (ZSD). The three cases showed distinct clinical features. Thus, expanding the phenotypic spectrum of PBDs and ascertaining exome sequencing is an effective strategy for an accurate diagnosis of clinically overlapping and genetically heterogeneous disorders such as deafness-blindness association.
本研究旨在对 3 名耳聋伴视网膜变性患者进行分子诊断。
对来自两个无血缘关系家庭的 3 名患者进行了初步分析，采用针对 Usher 基因、非综合征性听力损失或遗传性综合征性视网膜病变的定制基因 panel 进行检测，然后通过临床或全外显子组测序进一步研究。
研究发现了 3 名患者的 基因中可能存在致病性变异，该基因通常与过氧化物酶体生物发生障碍（PBD）有关。除了耳聋伴失明外，两个家系还存在其他特征：家系 1 的同胞表现为牙釉质改变和异常过氧化物酶体。此外，该兄弟还伴有轻度神经发育迟缓和肾结石。家系 2 的病例 II:1 表现为智力残疾、牙釉质改变和畸形。
本研究报道了 3 例新的 基因致病性变异病例，表现为更轻微的 Zellweger 谱障碍（ZSD）形式。这 3 个病例表现出不同的临床特征。因此，扩展 PBD 的表型谱并进行外显子组测序是一种有效的策略，可用于对临床上重叠且遗传异质性的疾病（如耳聋伴失明）进行准确诊断。
