title: Molecular genetic testing in clinical diagnostic assessments that demonstrate correlations in patients with autosomal recessive inherited retinal dystrophy.
abstract: OBJECTIVE
  Inherited retinal dystrophies (IRDs) are a group of retinal degenerative diseases presenting genetic and clinical heterogeneities, which have challenged the genetic and clinical diagnoses of IRDs. Genetic evaluations of patients with IRD might result in better clinical assessments and better management of patients.
  
  
  OBJECTIVE
  To determine the genetic lesions with phenotypic correlations in patients with diverse autosomal recessive IRD using next-generation sequencing.
  
  
  METHODS
  A cohort of 20 Chinese families affected with autosomal recessive IRD were recruited (with data on their detailed family history and on their clinical condition). To identify disease-causing mutations in the patients, the targeted sequence capture of IRD-relevant genes using 2 in-house-designed microarrays, followed by next-generation sequencing, was performed. Bioinformatics annotation, intrafamilial cosegregation analyses, in silico analyses, and functional analyses were subsequently conducted for the variants identified by next-generation sequencing.
  
  
  METHODS
  The results of detailed clinical evaluations, the identification of disease-causing mutations, and the clinical diagnosis.
  
  
  RESULTS
  Homozygous and biallelic variants were identified in 11 of the 20 families (55%) as very likely disease-causing mutations, including a total of 17 alleles, of which 12 are novel. The 17 alleles identified here include 3 missense, 6 nonsense, 4 frameshift, and 4 splice site mutations. In addition, we found biallelic RP1 mutations in a patient with cone-rod dystrophy, which was not previously correlated with RP1 mutations. Moreover, the identification of pathogenic mutations in 3 families helped to refine their clinical diagnoses.
  
  
  CONCLUSIONS
  In this study, to our knowledge, many mutations identified in those known loci for autosomal recessive IRD are novel. Specific RP1 mutations may correlate with cone-rod dystrophy. Genetic evaluations with targeted next-generation sequencing might result in a better clinical diagnosis and a better clinical assessment and, therefore, should be recommended for such patients.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong Province, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong Province, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Guan
authors.affiliation: Tianjin Medical University, Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, China.
authors.forename: Kanxing
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China4Department of Ophthalmology, The Affiliated Jiangyin Hospital of Southeast University Medical College.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, School of Medicine, Henan Polytechnic University, Henan, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Gu
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong Province, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong Province, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong Province, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, School of Medicine, Henan Polytechnic University, Henan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Kang
authors.affiliation: Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
authors.forename: Xunlun
authors.initials: X
authors.lastname: Sheng
authors.affiliation: The First Clinical Medical College of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China9State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat Sen University, Guangzhou.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D058499:Retinal Dystrophies / Q000175:diagnosis* / Q000235:genetics*; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: D005136:Eye Proteins; D005819:Genetic Markers