Phenotypic spectrum and prevalence of INPP5E mutations in Joubert Syndrome and related disorders

International JSRD Study Group

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47 Scopus citations


Joubert syndrome and related disorders (JSRD) are clinically and genetically heterogeneous ciliopathies sharing a peculiar midbrain-hindbrain malformation known as the 'molar tooth sign'. To date, 19 causative genes have been identified, all coding for proteins of the primary cilium. There is clinical and genetic overlap with other ciliopathies, in particular with Meckel syndrome (MKS), that is allelic to JSRD at nine distinct loci. We previously identified the INPP5E gene as causative of JSRD in seven families linked to the JBTS1 locus, yet the phenotypic spectrum and prevalence of INPP5E mutations in JSRD and MKS remain largely unknown. To address this issue, we performed INPP5E mutation analysis in 483 probands, including 408 JSRD patients representative of all clinical subgroups and 75 MKS fetuses. We identified 12 different mutations in 17 probands from 11 JSRD families, with an overall 2.7% mutation frequency among JSRD. The most common clinical presentation among mutated families (7/11, 64%) was Joubert syndrome with ocular involvement (either progressive retinopathy and/or colobomas), while the remaining cases had pure JS. Kidney, liver and skeletal involvement were not observed. None of the MKS fetuses carried INPP5E mutations, indicating that the two ciliopathies are not allelic at this locus.

Original languageEnglish (US)
Pages (from-to)1074-1078
Number of pages5
JournalEuropean Journal of Human Genetics
Issue number10
StatePublished - Oct 1 2013

Bibliographical note

Funding Information:
This work was partly supported with grants from the Italian Ministry of Health (Ricerca Corrente 2012 to EMV, Ricerca Finalizzata 2009 to EB and EMV), the Italian Telethon Foundation (GGP08045 to EB and EMV), the European Research Council (Starting Grant 260888 to EMV), the National Institute of Health (R01NS048453 to JGG), the Broad Institute (U54HG003067 to Eric Lander) for sequencing support and analysis. We thank Dr Celine Gomes and Professor Arnold Munnich for referring patients.


  • INPP5E
  • Joubert syndrome and related disorders
  • Meckel syndrome
  • ciliopathies


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