title: Phenotypic spectrum and prevalence of INPP5E mutations in Joubert syndrome and related disorders.
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.
authors: 1] IRCCS Casa Sollievo della Sofferenza, Mendel Laboratory San Giovanni Rotondo, San Giovanni Rotondo, Italy [2] Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors: Lorena
authors: L
authors: Travaglini
authors: Francesco
authors: F
authors: Brancati
authors: Jennifer
authors: J
authors: Silhavy
authors: Miriam
authors: M
authors: Iannicelli
authors: Elizabeth
authors: E
authors: Nickerson
authors: Nadia
authors: N
authors: Elkhartoufi
authors: Eric
authors: E
authors: Scott
authors: Emily
authors: E
authors: Spencer
authors: Stacey
authors: S
authors: Gabriel
authors: Sophie
authors: S
authors: Thomas
authors: Bruria
authors: B
authors: Ben-Zeev
authors: Enrico
authors: E
authors: Bertini
authors: Eugen
authors: E
authors: Boltshauser
authors: Malika
authors: M
authors: Chaouch
authors: Maria Roberta
authors: MR
authors: Cilio
authors: Mirjam M
authors: MM
authors: de Jong
authors: Hulya
authors: H
authors: Kayserili
authors: Gonul
authors: G
authors: Ogur
authors: Andrea
authors: A
authors: Poretti
authors: Sabrina
authors: S
authors: Signorini
authors: Graziella
authors: G
authors: Uziel
authors: Maha S
authors: MS
authors: Zaki
authors: Colin
authors: C
authors: Johnson
authors: Tania
authors: T
authors: Attié-Bitach
authors: Joseph G
authors: JG
authors: Gleeson
authors: Enza Maria
authors: EM
authors: Valente
mesh_terms: D000015:Abnormalities, Multiple; D000293:Adolescent; D000595:Amino Acid Sequence; D002526:Cerebellar Diseases / Q000175:diagnosis / Q000235:genetics*; D002531:Cerebellum / Q000002:abnormalities; D002648:Child; D002675:Child, Preschool; D002925:Ciliary Motility Disorders / Q000175:diagnosis / Q000235:genetics; D004677:Encephalocele / Q000175:diagnosis / Q000235:genetics; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D007223:Infant; D052177:Kidney Diseases, Cystic / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D007690:Polycystic Kidney Diseases / Q000175:diagnosis / Q000235:genetics; D011296:Prenatal Diagnosis; D015995:Prevalence; D012160:Retina / Q000002:abnormalities*; D012174:Retinitis Pigmentosa; D000099182:Phosphoinositide 5-Phosphatases
chemical_list: D010744:Phosphoric Monoester Hydrolases; D000099182:Phosphoinositide 5-Phosphatases
references: Nat Genet. 2011 Mar;43(3):189-96
references: 21258341
references: Nat Genet. 2010 Feb;42(2):175-80
references: 20081859
references: Cell. 2011 Sep 30;147(1):70-9
references: 21962508
references: Nat Genet. 2010 Jul;42(7):619-25
references: 20512146
references: Neuropediatrics. 2009 Dec;40(6):287-90
references: 20446224
references: Orphanet J Rare Dis. 2010 Jul 08;5:20
references: 20615230
references: Nat Genet. 2011 May;43(5):491-8
references: 21478889
references: J Med Genet. 2012 Feb;49(2):126-37
references: 22241855
references: Science. 2001 Sep 21;293(5538):2256-9
references: 11567139
references: Am J Hum Genet. 2007 Jul;81(1):104-13
references: 17564967
references: Cell. 2012 Aug 3;150(3):533-48
references: 22863007
references: Am J Med Genet A. 2009 Oct;149A(10):2173-80
references: 19764032
references: Am J Med Genet. 1984 Aug;18(4):671-89
references: 6486167
references: J Med Genet. 2012 Oct;49(10):636-41
references: 23012439
references: Hum Mutat. 2010 May;31(5):E1319-31
references: 20232449
references: Nat Genet. 2007 Jul;39(7):882-8
references: 17558407
references: Nat Genet. 2009 Jun;41(6):739-45
references: 19430481
references: Subcell Biochem. 2012;58:215-79
references: 22403078
references: J Med Genet. 2010 Jan;47(1):8-21
references: 19574260
references: J Med Genet. 2005 Feb;42(2):e9
references: 15689444
references: Hum Mutat. 2009 Feb;30(2):E432-42
references: 19058225
references: Am J Hum Genet. 2012 Aug 10;91(2):372-8
references: 22883145
references: Am J Hum Genet. 2008 Aug;83(2):170-9
references: 18674751
references: Nat Genet. 2009 Sep;41(9):1032-6
references: 19668216
references: Nat Genet. 2012 Jan 15;44(2):193-9
references: 22246503
references: Ann Neurol. 2006 Mar;59(3):527-34
references: 16453322
references: Nat Genet. 2009 Sep;41(9):1027-31
references: 19668215