title: Exome sequencing identifies a homozygous C5orf42 variant in a Turkish kindred with oral-facial-digital syndrome type VI.
abstract: Oral-facial-digital syndrome type VI (OFDVI) is a rare ciliopathy in the spectrum of Joubert syndrome (JS) and distinguished from other oral-facial-digital syndromes by metacarpal abnormalities with central polydactyly and by a molar tooth sign on cranial MRI. Additional characteristic features include short stature, micrognathia, posteriorly rotated low-set ears, hypertelorism, epicanthal folds, broad nasal tip, tongue hamartoma, upper lip notch, intraoral frenula, cleft lip/palate, and renal anomalies. Recently, novel mutations in C5orf42 were identified in 9 out of 11 OFDVI families. In a subsequent study C5orf42 was found to be mutated in only 2 out of 17 OFDVI probands while 28 patients with a pure JS phenotype also had pathogenic mutations of C5orf42. We report on two affected cousins diagnosed with OFDVI who were born from first degree cousin marriages. Whole exome sequencing (WES) identified a homozygous predicted damaging missense mutation (c.4034A > G; p.Gln1345Arg) in the C5orf42 gene. Our data contribute to the evidence that C5orf42 is one of the causative genes for OFDVI.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Bayram
authors.affiliation: Center of Genetics Diagnosis, Zeynep Kamil Women's and Children's Diseases Training and Research Hospital, Istanbul, Turkey.
authors.forename: Hatip
authors.initials: H
authors.lastname: Aydin
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gambin
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Zeynep Coban
authors.initials: ZC
authors.lastname: Akdemir
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Mehmed M
authors.initials: MM
authors.lastname: Atik
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Ender
authors.initials: E
authors.lastname: Karaca
authors.affiliation: Center of Genetics Diagnosis, Zeynep Kamil Women's and Children's Diseases Training and Research Hospital, Istanbul, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Karaman
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Davut
authors.initials: D
authors.lastname: Pehlivan
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Shalini N
authors.initials: SN
authors.lastname: Jhangiani
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas.|Texas Children's Hospital, Houston, Texas.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D002526:Cerebellar Diseases / Q000235:genetics; D002531:Cerebellum / Q000002:abnormalities; D002648:Child; D002972:Cleft Palate / Q000235:genetics; D059472:Exome / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006222:Hamartoma / Q000235:genetics; D006720:Homozygote; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009958:Orofaciodigital Syndromes / Q000235:genetics*; D010641:Phenotype; D012160:Retina / Q000002:abnormalities; D014421:Turkey
chemical_list: C572460:CPLANE1 protein, human; D008565:Membrane Proteins
keywords: C5orf42; ciliopathy; oral-facial-digital syndrome type VI
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