Exome sequencing identifies a homozygous C5orf42 variant in a Turkish kindred with oral‐facial‐digital syndrome type VI. (6th April 2015)

• Record Type: Journal Article
• Authors: Bayram, Yavuz; Aydin, Hatip; Gambin, Tomasz; Akdemir, Zeynep Coban; Atik, Mehmed M.; Karaca, Ender; Karaman, Ali; Pehlivan, Davut; Jhangiani, Shalini N.; Gibbs, Richard A.; Lupski, James R.
• Is Part Of: American journal of medical genetics. Volume 167:Number 9(2015:Sep.)
• Page Start: 2132
• Page End: 2137
• Publication Date: 2015-04-06
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.37092
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga37092-sec-0001" sec-type="section"> <p>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 <italic>C5orf42</italic> were identified in 9 out of 11 OFDVI families. In a subsequent study <italic>C5orf42</italic> 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 <italic>C5orf42</italic>.</p> <p>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 &gt; G; p.Gln1345Arg) in the <italic>C5orf42</italic> gene. Our data contribute to the evidence that <italic>C5orf42</italic> is one of the causative genes for OFDVI. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>