Novel mutations in CRB1 gene identified in a chinese pedigree with retinitis pigmentosa by targeted capture and next generation sequencing.
OBJECTIVE
To detect the disease-causing gene in a Chinese pedigree with autosomal-recessive retinitis pigmentosa (ARRP).


METHODS
All subjects in this family underwent a complete ophthalmic examination. Targeted-capture next generation sequencing (NGS) was performed on the proband to detect variants. All variants were verified in the remaining family members by PCR amplification and Sanger sequencing.


RESULTS
All the affected subjects in this pedigree were diagnosed with retinitis pigmentosa (RP). The compound heterozygous c.138delA (p.Asp47IlefsX24) and c.1841G>T (p.Gly614Val) mutations in the Crumbs homolog 1 (CRB1) gene were identified in all the affected patients but not in the unaffected individuals in this family. These mutations were inherited from their parents, respectively.


CONCLUSIONS
The novel compound heterozygous mutations in CRB1 were identified in a Chinese pedigree with ARRP using targeted-capture next generation sequencing. After evaluating the significant heredity and impaired protein function, the compound heterozygous c.138delA (p.Asp47IlefsX24) and c.1841G>T (p.Gly614Val) mutations are the causal genes of early onset ARRP in this pedigree. To the best of our knowledge, there is no previous report regarding the compound mutations.
Department of Ophthalmology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
Lan
L
Lu
Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, Guangdong, 518000, China.
Xizhen
X
Wang
Department of Internal Medicine, Danbury, CT 06810, USA.
David
D
Lo
Department of Ophthalmology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
Jingning
J
Weng
Department of Ophthalmology, The People's Hospital of Baoan Shenzhen, Guangdong, 518101, China.
Xiaohong
X
Liu
Biomedical Engineering Center, Fujian Medical University, Fuzhou, Fujian, 350001, China.
Juhua
J
Yang
Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, Guangdong, 518000, China.
Fen
F
He
Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, Guangdong, 518000, China.
Yun
Y
Wang
Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, Guangdong, 518000, China.
Xuyang
X
Liu
D000293:Adolescent; D044466:Asian People / Q000235:genetics; D002681:China; D004252:DNA Mutational Analysis / Q000379:methods; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005808:Genes, Recessive; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D041623:Tomography, Optical Coherence
C448939:CRB1 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins
mutation; next generation sequencing; pedigree; retinitis pigmentosa