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Exome sequencing identifies novel mutations in C5orf42 in patients with Joubert syndrome with oral-facial-digital anomalies.

ABSTRACT: Oral-facial-digital syndrome VI (OFD6 OMIM #277170), also called Varadi-Papp syndrome, is a ciliopathy inherited in an autosomal recessive pattern. Recently, mutations in C5orf42 (OMIM #614571) have been associated with OFD6. OFD6 overlaps with Joubert syndrome and mutations in C5orf42 were described in Joubert syndrome 17 (JBTS17, OMIM #614571). Using exome sequencing we report three novel variants and one previously reported variant in the C5orf42 gene in patients with OFD6.

SUBMITTER: Wentzensen IM

PROVIDER: S-EPMC4785546 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Exome sequencing identifies novel mutations in C5orf42 in patients with Joubert syndrome with oral-facial-digital anomalies.

Wentzensen Ingrid M IM Johnston Jennifer J JJ Keppler-Noreuil Kim K Acrich Karina K David Karen K Johnson Kisha D KD Graham John M JM Sapp Julie C JC Biesecker Leslie G LG

Human genome variation 20151119

Oral-facial-digital syndrome VI (OFD6 OMIM #277170), also called Varadi-Papp syndrome, is a ciliopathy inherited in an autosomal recessive pattern. Recently, mutations in C5orf42 (OMIM #614571) have been associated with OFD6. OFD6 overlaps with Joubert syndrome and mutations in C5orf42 were described in Joubert syndrome 17 (JBTS17, OMIM #614571). Using exome sequencing we report three novel variants and one previously reported variant in the C5orf42 gene in patients with OFD6. ...[more]

PMID: 27081551

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Exome sequencing identifies a homozygous C5orf42 variant in a Turkish kindred with oral-facial-digital syndrome type VI.

Project description: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.

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Oral-facial-digital syndrome type VI: is C5orf42 really the major gene?

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Mutations in C5ORF42 cause Joubert syndrome in the French Canadian population.

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