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

International JSRD Study Group

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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
Pages (from-to)1074-1078
Number of pages5
JournalEuropean Journal of Human Genetics
Volume21
Issue number10
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Mutation
Fetus
Coloboma
Patient Advocacy
Rhombencephalon
Joubert syndrome 1
Cilia
Mutation Rate
Mesencephalon
Genes
Tooth
Kidney
Meckel syndrome type 1
Liver
Ciliopathies
Proteins

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Phenotypic spectrum and prevalence of INPP5E mutations in Joubert Syndrome and related disorders. / International JSRD Study Group.

In: European Journal of Human Genetics, Vol. 21, No. 10, 2013, p. 1074-1078.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Ogur, Gonul

AU - Poretti, Andrea

AU - Signorini, Sabrina

AU - Uziel, Graziella

AU - Zaki, Maha S.

AU - Johnson, Colin

AU - Attié-Bitach, Tania

AU - Gleeson, Joseph G.

AU - Valente, Enza Maria

AU - Ali Pacha, L.

AU - Zankl, A.

AU - Leventer, R.

AU - Grattan-Smith, P.

AU - Janecke, A.

AU - Koch, J.

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AU - Demerleir, L.

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AU - Moreira, A.

AU - Ae Kim, C.

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AU - Dakovic, I.

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N2 - 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.

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KW - Meckel syndrome

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