title: Novel mutation in the CHST6 gene causes macular corneal dystrophy in a black South African family.
abstract: Macular corneal dystrophy (MCD) is a rare autosomal recessive disorder that is characterized by progressive corneal opacity that starts in early childhood and ultimately progresses to blindness in early adulthood. The aim of this study was to identify the cause of MCD in a black South African family with two affected sisters.
  
  
  
  A multigenerational South African Sotho-speaking family with type I MCD was studied using whole exome sequencing. Variant filtering to identify the MCD-causal mutation included the disease inheritance pattern, variant minor allele frequency and potential functional impact.
  
  
  
  Ophthalmologic evaluation of the cases revealed a typical MCD phenotype and none of the other family members were affected. An average of 127 713 variants per individual was identified following exome sequencing and approximately 1.2 % were not present in any of the investigated public databases. Variant filtering identified a homozygous E71Q mutation in CHST6, a known MCD-causing gene encoding corneal N-acetyl glucosamine-6-O-sulfotransferase. This E71Q mutation results in a non-conservative amino acid change in a highly conserved functional domain of the human CHST6 that is essential for enzyme activity.
  
  
  
  We identified a novel E71Q mutation in CHST6 as the MCD-causal mutation in a black South African family with type I MCD. This is the first description of MCD in a black Sub-Saharan African family and therefore contributes valuable insights into the genetic aetiology of this disease, while improving genetic counselling for this and potentially other MCD families.
authors.affiliation: Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, 2050, Johannesburg, Gauteng, South Africa.
authors.forename: Nadia
authors.initials: N
authors.lastname: Carstens
authors.affiliation: Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Susan
authors.initials: S
authors.lastname: Williams
authors.affiliation: Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Saadiah
authors.initials: S
authors.lastname: Goolam
authors.affiliation: Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Trevor
authors.initials: T
authors.lastname: Carmichael
authors.affiliation: Biomarker Development, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Ming Sin
authors.initials: MS
authors.lastname: Cheung
authors.affiliation: Biomarker Development, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Stine
authors.initials: S
authors.lastname: Büchmann-Møller
authors.affiliation: Biomarker Development, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Sultan
authors.affiliation: Biomarker Development, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Staedtler
authors.affiliation: Center for Proteomic Chemistry, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Chao
authors.initials: C
authors.lastname: Zou
authors.affiliation: Division of Anatomical Pathology, National Health Laboratory Services and University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Peter
authors.initials: P
authors.lastname: Swart
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, USA.
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Rice
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, USA.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lacoste
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Paes
authors.affiliation: Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, 2050, Johannesburg, Gauteng, South Africa. michele.ramsay@wits.ac.za.|Division of Human Genetics, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, 2050, Johannesburg, Gauteng, South Africa. michele.ramsay@wits.ac.za.
authors.forename: Michèle
authors.initials: M
authors.lastname: Ramsay
mesh_terms: D000328:Adult; D003315:Cornea / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013019:South Africa; D015238:Sulfotransferases / Q000235:genetics*; D000097811:Carbohydrate Sulfotransferases
chemical_list: D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases
keywords: African; CHST6; Macular corneal dystrophy; Whole exome sequencing