PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Whole exome sequencing unveils a frameshift mutation in CNGB3 for cone dystrophy: A case report of an Indian family.

Abstract Genetic elucidation of cone-dominated retinal dystrophies in Indian subcontinent is much needed to identify and catalog underlying genetic defects. In this context, the present study recruited a consanguineous Indian family affected with autosomal recessive cone dystrophy (CD). Considering the huge genetic heterogeneity and recessive inheritance of the disease, we chose to dissect out causal variant in this family by whole exome sequencing (WES).
PMID
Related Publications

Identification of a novel mutation in the CDHR1 gene in a family with recessive retinal degeneration.

Comprehensive analysis of the achromatopsia genes CNGA3 and CNGB3 in progressive cone dystrophy.

Novel CNGA3 and CNGB3 mutations in two Pakistani families with achromatopsia.

CNGB3 achromatopsia with progressive loss of residual cone function and impaired rod-mediated function.

Progressive cone dystrophy associated with mutation in CNGB3.

Authors

Mayor MeshTerms

Frameshift Mutation

Siblings

Keywords
Journal Title medicine
Publication Year Start




PMID- 28746191
OWN - NLM
STAT- MEDLINE
DA  - 20170726
DCOM- 20170807
LR  - 20170807
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Linking)
VI  - 96
IP  - 30
DP  - 2017 Jul
TI  - Whole exome sequencing unveils a frameshift mutation in CNGB3 for cone dystrophy:
      A case report of an Indian family.
PG  - e7490
LID - 10.1097/MD.0000000000007490 [doi]
AB  - RATIONALE: Genetic elucidation of cone-dominated retinal dystrophies in Indian
      subcontinent is much needed to identify and catalog underlying genetic defects.
      In this context, the present study recruited a consanguineous Indian family
      affected with autosomal recessive cone dystrophy (CD). Considering the huge
      genetic heterogeneity and recessive inheritance of the disease, we chose to
      dissect out causal variant in this family by whole exome sequencing (WES).
      PATIENT CONCERNS: In the recruited family, three of the six siblings had
      complaints of poor visual acuity, photophobia, and disturbed colour vision since 
      early childhood. Fundus examination disclosed vascular attenuation and macular
      retinal pigment epithelium (RPE) changes in all the affected siblings, signifying
      degeneration of photoreceptor cells. DIAGNOSIS: Complete clinical investigation
      and electroretinography studies led to the diagnosis of cone dystrophy in three
      siblings of the family. INTERVENTIONS: Detailed ophthalmic examination, including
      family history, visual function testing, and retinal imaging, was performed. We
      captured and sequenced exomes of 2 affected siblings and their mother using
      SureSelect Human All Exon V5 Kit on Illumina HiSeq 2000/2500 platform with 100 bp
      paired-end sequencing method. Candidates after data analysis were screened by
      segregation analysis and Sanger sequencing. Considering recessive inheritance and
      consanguinity in the pedigree, we attempted to map large loci homozygous by
      descent in the genome of patients using exome sequencing variants. Extensive
      protein modeling was carried out to assess possible consequences of the
      identified variant on the 3-dimensional structure of the protein. OUTCOMES: WES
      generated more than 65,000 variants for each individual. Assuming recessive
      inheritance, 13,026 variants were selected. Further filtering on the basis of
      their position in gene, class, and minor allele frequency constricted the huge
      list to 12 rare variants. Finally, we ascertained a single base deletion
      c.1148delC (p.Thr383fs) in the gene CNGB3 as the causal variant. This is a
      recurrent frameshift mutation resulting in truncated CNGB3 protein. We mapped a
      large 15-Mb stretch of homozygous markers spanning the causal variant in the
      proband. The gene CNGB3 encodes modulatory subunit of cyclic nucleotide-gated
      channels in cone photoreceptors. Protein modeling reveals loss of 2 transmembrane
      helices and conserved CAP_ED domain in truncated CNGB3, which eventually is
      predicted to form nonfunctional channels and hamper phototransduction. LESSONS:
      We have identified a recurrent mutation c.1148delC (p.Thr383fs) in CNGB3 for
      autosomal recessive CD. The present report provides the first description of
      CNGB3 mutation from India. It is also the foremost investigation of familial CD
      in Indian patients; therefore, it presents the primary genetic etiology of CD in 
      India.
FAU - Gupta, Shashank
AU  - Gupta S
AD  - aDepartment of Molecular and Human Genetics, Institute of Science, Banaras Hindu 
      University, Varanasi, Uttar Pradesh bPremas Life Sciences Private Limited, Delhi 
      cDepartment of Bioinformatics, Mahila Maha Vidyalaya, Banaras Hindu University
      dR. K. Netralaya Eye Hospital and Research Centre, Varanasi, Uttar Pradesh,
      India.
FAU - Chaurasia, Amit
AU  - Chaurasia A
FAU - Pathak, Ekta
AU  - Pathak E
FAU - Mishra, Rajeev
AU  - Mishra R
FAU - Chaudhry, Vidya Nair
AU  - Chaudhry VN
FAU - Chaudhry, Prashaant
AU  - Chaudhry P
FAU - Mukherjee, Ashim
AU  - Mukherjee A
FAU - Mutsuddi, Mousumi
AU  - Mutsuddi M
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (CNGB3 protein, human)
RN  - 0 (Cyclic Nucleotide-Gated Cation Channels)
SB  - AIM
SB  - IM
MH  - Adolescent
MH  - Child
MH  - Cyclic Nucleotide-Gated Cation Channels/*genetics/metabolism
MH  - Exome
MH  - Female
MH  - *Frameshift Mutation
MH  - Homozygote
MH  - Humans
MH  - India
MH  - Models, Molecular
MH  - Retinal Degeneration/*genetics/physiopathology
MH  - *Siblings
EDAT- 2017/07/27 06:00
MHDA- 2017/08/08 06:00
CRDT- 2017/07/27 06:00
AID - 10.1097/MD.0000000000007490 [doi]
AID - 00005792-201707280-00022 [pii]
PST - ppublish
SO  - Medicine (Baltimore). 2017 Jul;96(30):e7490. doi: 10.1097/MD.0000000000007490.