C5orf42 is the major gene responsible for OFD syndrome type VI

Hum Genet. 2014 Mar;133(3):367-77. doi: 10.1007/s00439-013-1385-1. Epub 2013 Nov 1.

Abstract

Oral-facial-digital syndrome type VI (OFD VI) is a recessive ciliopathy defined by two diagnostic criteria: molar tooth sign (MTS) and one or more of the following: (1) tongue hamartoma (s) and/or additional frenula and/or upper lip notch; (2) mesoaxial polydactyly of one or more hands or feet; (3) hypothalamic hamartoma. Because of the MTS, OFD VI belongs to the "Joubert syndrome related disorders". Its genetic aetiology remains largely unknown although mutations in the TMEM216 gene, responsible for Joubert (JBS2) and Meckel-Gruber (MKS2) syndromes, have been reported in two OFD VI patients. To explore the molecular cause(s) of OFD VI syndrome, we used an exome sequencing strategy in six unrelated families followed by Sanger sequencing. We identified a total of 14 novel mutations in the C5orf42 gene in 9/11 families with positive OFD VI diagnostic criteria including a severe fetal case with microphthalmia, cerebellar hypoplasia, corpus callosum agenesis, polydactyly and skeletal dysplasia. C5orf42 mutations have already been reported in Joubert syndrome confirming that OFD VI and JBS are allelic disorders, thus enhancing our knowledge of the complex, highly heterogeneous nature of ciliopathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple
  • Adolescent
  • Adult
  • Alleles
  • Cerebellar Diseases / diagnosis
  • Cerebellar Diseases / genetics
  • Cerebellum / abnormalities
  • Child
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics
  • Exome
  • Eye Abnormalities / diagnosis
  • Eye Abnormalities / genetics
  • Female
  • Hamartoma / diagnosis
  • Hamartoma / genetics
  • Humans
  • Hypothalamic Diseases / diagnosis
  • Hypothalamic Diseases / genetics
  • Kidney Diseases, Cystic / diagnosis
  • Kidney Diseases, Cystic / genetics
  • Male
  • Membrane Proteins / genetics*
  • Mutation
  • Nervous System Malformations / diagnosis
  • Nervous System Malformations / genetics
  • Orofaciodigital Syndromes / diagnosis*
  • Orofaciodigital Syndromes / genetics*
  • Phenotype
  • Polydactyly / diagnosis
  • Polydactyly / genetics
  • Retina / abnormalities
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • CPLANE1 protein, human
  • Membrane Proteins

Supplementary concepts

  • Agenesis of Cerebellar Vermis
  • Cerebellar Hypoplasia
  • Hypothalamic hamartomas
  • Orofaciodigital syndrome 6