Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, NY, USA.
Laboratory of Personalized Genomic Medicine, Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Orphanet J Rare Dis. 2020 Nov 13;15(1):320. doi: 10.1186/s13023-020-01600-8.
Primary coenzyme Q10 deficiency is a rare disease that results in diverse and variable clinical manifestations. Nephropathy, myopathy and neurologic involvement are commonly associated, however retinopathy has also been observed with certain pathogenic variants of genes in the coenzyme Q biosynthesis pathway. In this report, we describe a novel presentation of the disease that includes nephropathy and retinopathy without neurological involvement, and which is the result of a compound heterozygous state arising from the inheritance of two recessive potentially pathogenic variants, previously not described.
Retrospective report, with complete ophthalmic examination, multimodal imaging, electroretinography, and whole exome sequencing performed on a family with three affected siblings.
We show that affected individuals in the described family inherited two heterozygous variants of the COQ2 gene, resulting in a frameshift variant in one allele, and a predicted deleterious missense variant in the second allele (c.288dupC,p.(Ala97Argfs*56) and c.376C > G,p.(Arg126Gly) respectively). Electroretinography results were consistent with rod-cone dystrophy in the affected individuals. All affected individuals in the family exhibited the characteristic retinopathy as well as end-stage nephropathy, without evidence of any neurological involvement.
We identified two novel compound heterozygous variants of the COQ2 gene that result in primary coenzyme Q deficiency. Targeted sequencing of coenzyme Q biosynthetic pathway genes may be useful in diagnosing oculorenal clinical presentations syndromes not explained by more well known syndromes (e.g., Senior-Loken and Bardet-Biedl syndromes).
原发性辅酶 Q10 缺乏症是一种罕见的疾病，可导致多种不同的临床表现。肾病、肌病和神经系统受累通常与之相关，但在辅酶 Q 生物合成途径的某些致病变体中也观察到了视网膜病变。在本报告中，我们描述了一种新的疾病表现形式，包括无神经系统受累的肾病和视网膜病变，其结果是由两种隐性潜在致病变体的复合杂合状态引起的，这两种变体以前未被描述过。
对一个受影响的三兄弟家庭进行回顾性报告，包括全面的眼科检查、多模态成像、视网膜电图和外显子组测序。
我们表明，所描述的家族中受影响的个体遗传了 COQ2 基因的两个杂合变体，导致一个等位基因的移码变体和第二个等位基因的预测有害错义变体（c.288dupC，p.（Ala97Argfs*56）和 c.376C> G，p.（Arg126Gly））。受影响个体的视网膜电图结果与视杆-视锥营养不良一致。该家族的所有受影响个体均表现出特征性的视网膜病变和终末期肾病，没有任何神经系统受累的证据。
我们鉴定了 COQ2 基因的两个新的复合杂合变体，导致原发性辅酶 Q10 缺乏症。针对辅酶 Q 生物合成途径基因的靶向测序可能有助于诊断无法用更知名综合征（如 Senior-Loken 和 Bardet-Biedl 综合征）解释的眼肾临床表现综合征。
