title: Novel C8orf37 mutations cause retinitis pigmentosa in consanguineous families of Pakistani origin.
abstract: OBJECTIVE
  To investigate the molecular basis of retinitis pigmentosa in two consanguineous families of Pakistani origin with multiple affected members.
  
  
  METHODS
  Homozygosity mapping and Sanger sequencing of candidate genes were performed in one family while the other was analyzed with whole exome next-generation sequencing. A minigene splicing assay was used to confirm the splicing defects.
  
  
  RESULTS
  In family MA48, a novel homozygous nucleotide substitution in C8orf37, c.244-2A>C, that disrupted the consensus splice acceptor site of exon 3 was found. The minigene splicing assay revealed that this mutation activated a cryptic splice site within exon 3, causing a 22 bp deletion in the transcript that is predicted to lead to a frameshift followed by premature protein truncation. In family MA13, a novel homozygous null mutation in C8orf37, c.555G>A, p.W185*, was identified. Both mutations segregated with the disease phenotype as expected in a recessive manner and were absent in 8,244 unrelated individuals of South Asian origin.
  
  
  CONCLUSIONS
  In this report, we describe C8orf37 mutations that cause retinal dystrophy in two families of Pakistani origin, contributing further data on the phenotype and the spectrum of mutations in this form of retinitis pigmentosa.
authors: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan ; Molecular Genetics Laboratory, Institute of Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors: Zeinab
authors: Z
authors: Ravesh
authors: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, UK ; Department of Zoology, Faculty of Science, Benha University, Benha, Egypt.
authors: Mohammed E
authors: ME
authors: El Asrag
authors: Molecular Genetics Laboratory, Institute of Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors: Nicole
authors: N
authors: Weisschuh
authors: The Eye Department, St. James's University Hospital, Leeds, UK.
authors: Martin
authors: M
authors: McKibbin
authors: Molecular Genetics Laboratory, Institute of Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors: Peggy
authors: P
authors: Reuter
authors: Yorkshire Regional Genetics Service, St. James's University Hospital, Leeds, UK.
authors: Christopher M
authors: CM
authors: Watson
authors: Molecular Genetics Laboratory, Institute of Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors: Britta
authors: B
authors: Baumann
authors: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, UK.
authors: James A
authors: JA
authors: Poulter
authors: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors: Sundus
authors: S
authors: Sajid
authors: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, UK.
authors: Evangelia S
authors: ES
authors: Panagiotou
authors: Manchester Centre for Genomic Medicine, University of Manchester, St Mary's Hospital, Manchester, UK.
authors: James
authors: J
authors: O'Sullivan
authors: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, UK.
authors: Zakia
authors: Z
authors: Abdelhamed
authors: Department of Medical Genetics, Angewandte Genomik, University of Tübingen, Tübingen, Germany.
authors: Michael
authors: M
authors: Bonin
authors: Department of Ophthalmology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan.
authors: Mehdi
authors: M
authors: Soltanifar
authors: Manchester Centre for Genomic Medicine, University of Manchester, St Mary's Hospital, Manchester, UK.
authors: Graeme C M
authors: GC
authors: Black
authors: Dera Ghazi Khan Campus, University of Education, Lahore, Pakistan.
authors: Muhammad
authors: M
authors: Amin-ud Din
authors: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, UK.
authors: Carmel
authors: C
authors: Toomes
authors: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors: Muhammad
authors: M
authors: Ansar
authors: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, UK.
authors: Chris F
authors: CF
authors: Inglehearn
authors: Molecular Genetics Laboratory, Institute of Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors: Bernd
authors: B
authors: Wissinger
authors: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, UK.
authors: Manir
authors: M
authors: Ali
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010154:Pakistan; D011506:Proteins / Q000235:genetics*; D012326:RNA Splicing; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology
chemical_list: D011506:Proteins; C570604:CFAP418 protein, human