Abstract
Purpose :
The purpose of the present study was to describe the molecular genetic mechanism and genotype-phenotype correlations in the mutation of Myosin VIIB gene (MYO7B), a new suspected pathogenic gene of retinal pigmentosa, within a Chinese family.
Methods :
Ophthalmologic examination and blood sample were obtained from RP probands and all available family members. Whole exon sequences were sequenced on an Illumina HiSeq 2000 machine. After sequencing, the reads were aligned to assembly hg19 of the human genome using BWA. Variant frequency data were obtained from public databases including the Exome Aggregation Consortium database, CHARGE consortium, ESP-6500, and 1000 Genomes Project. ANNOVAR and dbNSFP suite were used to annotate protein-altering effects. Reported retinal disease-causing variants were detected based on the HGMD professional database. The pathogenicity of variants was predicted by Scale-invariant feature transform, polymorphism phenotyping v2, likelihood-ratio test, MutationTaster, MutationAssessor and functional analysis through hidden Markov models as previously described. Mutation results were tested with all family members by Sanger sequencing. Crystallographic data were retrieved through UniProtKB/Swiss-Prot from the Protein Data Bank (PDB) and imported into the DeepView/Swiss-PdbViewer version 4.1.0. Structural analyses and visualizations were performed in project mode.
Results :
The proband had the onset of night blindness in the first decade of life. Ocular findings were characterized by diffuse retinal pigmentary degenerative changes, marked restriction of peripheral visual fields, severe loss of VA and posterior subcapsular lens opacities. The mutations of c.5899C>T(p.R1967C) and c.6347C>T(p.T2116I) in MYO7B gene was found in the proband, which were verified in other family members. No significant changes of protein conformation were found in homology modeling analysis，and the functional changes still need further study.
Conclusions :
MYO7B gene is found as a new suspected pathogenic gene associated with autosomal recessive retinitis pigmentosa, which has never been reported previously. The next generation sequencing technology is beneficial to the clinical diagnosis of hereditary eye diseases and has enriched the genetic database of retinal pigmentation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.