Genotype-phenotype correlation in CC2D2A-related Joubert syndrome reveals an association with ventriculomegaly and seizures

Ruxandra Bachmann-Gagescu, Gisele E. Ishak, Jennifer C. Dempsey, Jonathan Adkins, Diana O'Day, Ian G. Phelps, Meral Gunay-Aygun, Antonie Debra Kline, Krzysztof Szczaluba, Loreto Martorell, Abdulrahman Alswaid, Shatha Alrasheed, Shashidhar Pai, Louise Izatt, Anne Ronan, Melissa A. Parisi, Heather Mefford, Ian Glass, Dan Doherty

Research output: Contribution to journalArticle

Abstract

Background: Joubert syndrome (JS) is a ciliopathy characterised by a distinctive brain malformation (the 'molar tooth sign'), developmental delay, abnormal eye movements and abnormal breathing pattern. Retinal dystrophy, cystic kidney disease, liver fibrosis and polydactyly are variably present, resulting in significant phenotypic heterogeneity and overlap with other ciliopathies. JS is also genetically heterogeneous, resulting from mutations in 13 genes. These factors render clinical/molecular diagnosis and management challenging. CC2D2A mutations are a relatively common cause of JS and also cause Meckel syndrome. The clinical consequences of CC2D2A mutations in patients with JS have been incompletely reported. Methods: Subjects with JS from 209 families were evaluated to identify mutations in CC2D2A. Clinical and imaging features in subjects with CC2D2A mutations were compared with those in subjects without CC2D2A mutations and reports in the literature. Results: 10 novel CC2D2A mutations in 20 subjects were identified; a summary is provided of all published CC2D2A mutations. Subjects with CC2D2A-related JS were more likely to have ventriculomegaly (p

Original languageEnglish (US)
Pages (from-to)126-137
Number of pages12
JournalJournal of Medical Genetics
Volume49
Issue number2
DOIs
StatePublished - Feb 2012

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Genetic Association Studies
Seizures
Mutation
Retinal Dystrophies
Cystic Kidney Diseases
Polydactyly
Joubert syndrome 1
Dyskinesias
Eye Movements
Liver Cirrhosis
Tooth
Respiration
Brain
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Bachmann-Gagescu, R., Ishak, G. E., Dempsey, J. C., Adkins, J., O'Day, D., Phelps, I. G., ... Doherty, D. (2012). Genotype-phenotype correlation in CC2D2A-related Joubert syndrome reveals an association with ventriculomegaly and seizures. Journal of Medical Genetics, 49(2), 126-137. https://doi.org/10.1136/jmedgenet-2011-100552

Genotype-phenotype correlation in CC2D2A-related Joubert syndrome reveals an association with ventriculomegaly and seizures. / Bachmann-Gagescu, Ruxandra; Ishak, Gisele E.; Dempsey, Jennifer C.; Adkins, Jonathan; O'Day, Diana; Phelps, Ian G.; Gunay-Aygun, Meral; Kline, Antonie Debra; Szczaluba, Krzysztof; Martorell, Loreto; Alswaid, Abdulrahman; Alrasheed, Shatha; Pai, Shashidhar; Izatt, Louise; Ronan, Anne; Parisi, Melissa A.; Mefford, Heather; Glass, Ian; Doherty, Dan.

In: Journal of Medical Genetics, Vol. 49, No. 2, 02.2012, p. 126-137.

Research output: Contribution to journalArticle

Bachmann-Gagescu, R, Ishak, GE, Dempsey, JC, Adkins, J, O'Day, D, Phelps, IG, Gunay-Aygun, M, Kline, AD, Szczaluba, K, Martorell, L, Alswaid, A, Alrasheed, S, Pai, S, Izatt, L, Ronan, A, Parisi, MA, Mefford, H, Glass, I & Doherty, D 2012, 'Genotype-phenotype correlation in CC2D2A-related Joubert syndrome reveals an association with ventriculomegaly and seizures', Journal of Medical Genetics, vol. 49, no. 2, pp. 126-137. https://doi.org/10.1136/jmedgenet-2011-100552
Bachmann-Gagescu, Ruxandra ; Ishak, Gisele E. ; Dempsey, Jennifer C. ; Adkins, Jonathan ; O'Day, Diana ; Phelps, Ian G. ; Gunay-Aygun, Meral ; Kline, Antonie Debra ; Szczaluba, Krzysztof ; Martorell, Loreto ; Alswaid, Abdulrahman ; Alrasheed, Shatha ; Pai, Shashidhar ; Izatt, Louise ; Ronan, Anne ; Parisi, Melissa A. ; Mefford, Heather ; Glass, Ian ; Doherty, Dan. / Genotype-phenotype correlation in CC2D2A-related Joubert syndrome reveals an association with ventriculomegaly and seizures. In: Journal of Medical Genetics. 2012 ; Vol. 49, No. 2. pp. 126-137.
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