Abstract
Purpose :
To characterize the phenotype and report the genetic defects in three Chinese patients with biallelic variants of the PNPLA6 gene.
Methods :
Detailed clinical evaluations were performed. Whole-exome sequencing was used to identify the genetic causes of these disorders. Sanger sequencing validation and segregation analysis were applied to confirm the pathogenic variants and reverse transcription polymerase chain reaction (RT-PCR) was carried out to further characterize the mRNA change of selected splicing alteration.
Results :
Three patients from 3 unrelated families were enrolled. The ages of patients were 12, 28 and 28 years old respectively. Best corrected visual acuity (BCVA) ranged from 0.01 to 0.1. Three patients all presented severe chorioretinal dystrophy. Four novel and two reported pathogenic variants in PNPLA6 (GenBank: NM_001166111) were identified including three nonsynonymous variants (c.3134C>T, c.3436G>A and c.3547C>T) and three splicing variants (c.1841+3A>G, c.2212-10A>G and c.3846+1G>A). RT-PCR confirmed that the splicing variants indeed lead to abnormal splicing.
Conclusions :
PNPLA6-related disorders can present variable clinical manifestations and choroideremia-like retinal changes can be characteristic ocular features. Accurate genetic testing can help us make early diagnosis.
This is a 2020 ARVO Annual Meeting abstract.