Introduction

Biallelic mutations in neuraminidase 1 (NEU1) are associated with cherry-red spots. Whole genome sequencing contributes to eliminating pseudo-homozygous mutations when large-scale deletion of one allele in NEU1 and other genes occurs.

Patients and methods

Bilateral cherry-red spots in the macula were the only detectable sign in an 11-year-old girl with reduced visual acuity over the last two years. Targeted exome sequencing of genes for inherited eye diseases identified a homozygous c.544A>G (p.Ser182Gly) variation in the NEU1 gene. This variant was also present in her mother in the heterozygous state but not in her father. Whole genome sequencing identified a heterozygous 27.5 kb deletion involving the whole coding exons of NEU1 in her father. Sanger sequencing disclosed the breakpoint of the deletion. This heterozygous deletion was also detected in the patient, so the c.544A>G mutation should be heterozygous in the patient.

Conclusion

The results of this case remind us of the limitations of routine exome sequencing and the need to perform segregation studies and deletion/duplication analysis or WGS if parental studies do not support exome findings. In addition, patients with sialidosis may present with ocular manifestations without systemic signs early in the disease course.

中文翻译：

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模仿NEU1的纯合错义突变的杂合结构变异与仅在眼睛中表现出临床体征有关。

介绍

神经氨酸酶1（NEU1）中的双等位基因突变与樱桃红色斑点相关。当NEU1和其他基因中的一个等位基因发生大规模缺失时，全基因组测序有助于消除假纯合突变。

患者和方法

在过去的两年中，黄斑中的双樱桃红色斑点是在11岁女孩中唯一可检测到的体征，该女孩的视力下降。针对遗传眼疾确定了纯合c.544A> G（p.Ser182Gly）变异基因的外显子测序NEU1基因。该变体也以杂合状态存在于她的母亲中，但在她的父亲中不存在。全基因组测序鉴定出一个27.5 kb杂合缺失，涉及其父亲NEU1的整个编码外显子。Sanger测序揭示了缺失的断点。在患者中也检测到这种杂合缺失，因此c.544A> G突变在患者中应该是杂合的。

结论

这种情况的结果使我们想起了常规外显子组测序的局限性，如果父母的研究不支持外显子组的发现，则需要进行隔离研究和缺失/重复分析或WGS。另外，唾液酸中毒患者在疾病过程的早期可能会出现眼部症状而没有全身性体征。