Heterozygous structural variation mimicking homozygous missense mutations in NEU1 associated with presenting clinical signs in eyes alone

Biallelic mutations in neuraminidase 1 (<i>NEU1</i>) are associated with cherry-red spots. Whole genome sequencing contributes to eliminating pseudo-homozygous mutations when large-scale deletion of one allele in <i>NEU1</i> and other genes occurs. 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&gt;G (p.Ser182Gly) variation in the <i>NEU1</i> 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 <i>NEU1</i> in her father. Sanger sequencing disclosed the breakpoint of the deletion. This heterozygous deletion was also detected in the patient, so the c.544A&gt;G mutation should be heterozygous in the patient. 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.