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 language | English |
|---|---|
| Pages (from-to) | 1074-1078 |
| Number of pages | 5 |
| Journal | European Journal of Human Genetics |
| Volume | 21 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2013 |
Fingerprint
Keywords
- ciliopathies
- INPP5E
- Joubert syndrome and related disorders
- Meckel syndrome
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Phenotypic spectrum and prevalence of INPP5E mutations in Joubert Syndrome and related disorders. / Travaglini, Lorena; Brancati, Francesco; Silhavy, Jennifer; Iannicelli, Miriam; Nickerson, Elizabeth; Elkhartoufi, Nadia; Scott, Eric; Spencer, Emily; Gabriel, Stacey; Thomas, Sophie; Ben-Zeev, Bruria; Bertini, Enrico; Boltshauser, Eugen; Chaouch, Malika; Roberta Cilio, Maria; De Jong, Mirjam M.; Kayserili, Hulya; Ogur, Gonul; Poretti, Andrea; Signorini, Sabrina; Uziel, Graziella; Zaki, Maha S.; Johnson, Colin; Attié-Bitach, Tania; Gleeson, Joseph G.; Valente, Enza Maria.
In: European Journal of Human Genetics, Vol. 21, No. 10, 10.2013, p. 1074-1078.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phenotypic spectrum and prevalence of INPP5E mutations in Joubert Syndrome and related disorders
AU - Travaglini, Lorena
AU - Brancati, Francesco
AU - Silhavy, Jennifer
AU - Iannicelli, Miriam
AU - Nickerson, Elizabeth
AU - Elkhartoufi, Nadia
AU - Scott, Eric
AU - Spencer, Emily
AU - Gabriel, Stacey
AU - Thomas, Sophie
AU - Ben-Zeev, Bruria
AU - Bertini, Enrico
AU - Boltshauser, Eugen
AU - Chaouch, Malika
AU - Roberta Cilio, Maria
AU - De Jong, Mirjam M.
AU - Kayserili, Hulya
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
PY - 2013/10
Y1 - 2013/10
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.
AB - 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.
KW - ciliopathies
KW - INPP5E
KW - Joubert syndrome and related disorders
KW - Meckel syndrome
UR - http://www.scopus.com/inward/record.url?scp=84884592278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884592278&partnerID=8YFLogxK
U2 - 10.1038/ejhg.2012.305
DO - 10.1038/ejhg.2012.305
M3 - Article
C2 - 23386033
AN - SCOPUS:84884592278
VL - 21
SP - 1074
EP - 1078
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 10
ER -