title: Tectonic gene mutations in patients with Joubert syndrome.
abstract: So far very few patients with sequence variants in the closely related tectonic genes TCTN1-3 have been described. By multi-gene panel next-generation sequencing (NGS) in patients with Joubert syndrome, we identified two more patients and summarize what is currently known about the phenotypes associated with sequence variants in these genes. In a boy aged 12 years with intellectual disability and the classical molar tooth sign on MRI, a homozygous splice-site sequence variant in TCTN3 leading to in-frame skipping of exon 7 was detected. A previously described non-truncating sequence variant in TCTN3 was also associated with Joubert syndrome, whereas four truncating sequence variants were detected in patients with Meckel-Gruber or Mohr-Majewski syndrome. The second patient, a boy aged 7 years with severe psychomotor retardation, was found to carry a homozygous canonic splice-site sequence variant in TCTN2. So far, only three sequence variants associated with Joubert syndrome and two with Meckel-Gruber syndrome have been described in this gene. Reviewing the clinical data on patients with sequence variants in the tectonic genes TCTN1-3 reveals that all of them have a neurological phenotype with vermis hypoplasia or occipital encephalocele associated with severe intellectual disability in the surviving patients. In contrast, other features frequently seen in patients with ciliopathies such as nephronophthisis, liver fibrosis, retinal dystrophy or coloboma have not been reported. Our patients emphasize the usefulness and efficacy of a comprehensive NGS panel approach. A concise genetic diagnosis may help to prevent unnecessary investigations and improve the clinical management of these patients.
authors.affiliation: Department of Pediatrics and Pediatric Neurology, Georg August University, Göttingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Huppke
authors.affiliation: Department of Pediatrics and Pediatric Neurology, Georg August University, Göttingen, Germany.
authors.forename: Eike
authors.initials: E
authors.lastname: Wegener
authors.affiliation: Genetikum, Neu-Ulm, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Böhrer-Rabel
authors.affiliation: 1] Center for Human Genetics Bioscientia, Ingelheim, Germany [2] Institute of Human Genetics, Cologne University, Cologne, Germany.
authors.forename: Hanno J
authors.initials: HJ
authors.lastname: Bolz
authors.affiliation: Department of Human Genetics, Georg August University, Göttingen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zoll
authors.affiliation: Department of Pediatrics and Pediatric Neurology, Georg August University, Göttingen, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Gärtner
authors.affiliation: 1] Center for Human Genetics Bioscientia, Ingelheim, Germany [2] Department of Nephrology & Center for Clinical Research, University of Freiburg, Freiburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Bergmann
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D065814:Cerebellar Vermis / Q000473:pathology; D002531:Cerebellum / Q000002:abnormalities*; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D052177:Kidney Diseases, Cystic / Q000175:diagnosis / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011859:Radiography; D012160:Retina / Q000002:abnormalities*; D014070:Tooth / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C561092:TCTN2 protein, human; C575748:TCTN3 protein, human; C561486:Tctn1 protein, human