Mutations in<i>TMEM231</i>cause Joubert syndrome in French Canadians

Srour, Myriam; Hamdan, Fadi F.; Schwartzentruber, Jeremy; Patry, Lysanne; Ospina, Luis H.; Shevell, Michael; Désilets, Valerie; Dobrzeniecka, Sylvia; Mathonnet, Géraldine; Lemyre, Emmanuelle; Massicotte, Christine; Labuda, Damian; Amrom, Dina; Andermann, Eva; Sébire, Guillaume; Maranda, Bruno; Rouleau, Guy A.; Majewski, Jacek; Michaud, Jacques L.

doi:10.1136/jmedgenet-2012-101132

Cited by 68 publications

(53 citation statements)

References 20 publications

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“…Target enrichment was achieved using the Agilent SureSelect 50 Mb (V3) All Exon Kit and followed by sequencing (Illumina HiSeq), generating 414 Gbp of 100 base pair, paired-end reads per sample. Read alignment, variant calling, and annotation were done as outlined for previous Finding of Rare Disease Genes projects 6 …”

Section: Methodsmentioning

confidence: 99%

Meconium ileus in a Lebanese family secondary to mutations in the GUCY2C gene

et al. 2014

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Meconium ileus is most often associated with mutations in the CFTR gene; however recently, mutations in GUCY2C in the Bedouin population have also been shown to result in this phenotype. This gene codes for an intestinal transmembrane receptor that generates cyclic GMP, which activates cystic fibrosis transmembrane receptor. We report a third family that supports the association of variants in the GUCY2C gene with meconium ileus (MI). A Lebanese kindred was studied and individuals affected with MI had either homozygous or compound heterozygous variants in GUCY2C. The earliest manifestation of the affected individuals was the presence of second trimester fetal echogenic bowel, thus resulting in the expansion of the differential diagnosis of this ultrasound finding.

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Section: Methodsmentioning

confidence: 99%

Meconium ileus in a Lebanese family secondary to mutations in the GUCY2C gene

et al. 2014

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“…1 To date, up to 19 genes have been identified with either autosomal recessive (INPP5E, TMEM216, AHI1, NPHP1, CEP290, TMEM67, RPGRIP1L, ARL13B, CC2D2A, TTC21B, KIF7, TCTN1, TCTN2, TMEM237, CEP41, TMEM138, C5orf42, TMEM231) or X-linked inheritance (OFD1). 2,3 Intriguingly, all JSRD genes code for proteins of the primary cilium, making these disorders part of the expanding group of ciliopathies. 4 There is large clinical and genetic overlap between JSRD and other ciliopathies such as Meckel syndrome (MKS; MIM249000), isolated nephronophthisis (NPH; MIM256100) and Senior-Loken syndrome (MIM266900).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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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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“…Target enrichment was achieved using the Agilent SureSelect 50 Mb (V3) All Exon Kit and followed by sequencing (Illumina HiSeq 2000), generating >14 Gbp of 100 bp, paired-end reads per sample. Read alignment, variant calling and annotation were done as outlined for previous FORGE projects11 with a pipeline based on BWA (Burrows-Wheeler Aligner), Picard, Annovar, and custom annotation scripts. Variants were compared to those previously seen in the 1000 genomes phase 1 dataset (April 2012 release), the 6500 exomes of the National Heart, Lung, and Blood Institute (NHLBI) GO Exome Sequencing Project (ESP, Seattle, Washington, USA, data downloaded 3 October 2012), as well as in approximately 1000 exomes previously sequenced at the McGill University and Genome Quebec Innovation Centre.…”

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Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type spondylometaphyseal dysplasia

et al. 2014

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Our identification of truncating mutations in GPX4 in two families affected with SSMD supports the pathogenic role of mutated GPX4 in this very rare disease. GPX4 is a member of the glutathione peroxidase family of antioxidant defence enzymes and protects cells against membrane lipid peroxidation. GPX4 is essential for early embryo development, regulating anti-oxidative and anti-apoptotic activities. Our findings highlight the importance of this enzyme in development of the cardiac, nervous, and skeletal systems.

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Mutations inTMEM231cause Joubert syndrome in French Canadians

Cited by 68 publications

References 20 publications

Meconium ileus in a Lebanese family secondary to mutations in the GUCY2C gene

Meconium ileus in a Lebanese family secondary to mutations in the GUCY2C gene

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

Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type spondylometaphyseal dysplasia

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