Fifteen novel mutations in theJAGGED1 gene of patients with Alagille syndrome

Crosnier, Cécile; Driancourt, Catherine; Raynaud, Nicole; Hadchouel, Michelle; Meunier–Rotival, Michèle

doi:10.1002/1098-1004(2001)17:1<72::aid-humu11>3.0.co;2-u

Cited by 35 publications

(23 citation statements)

References 5 publications

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“…This screening has largely been performed using scanning techniques such as SSCP analysis, conformation sensitive gel electrophoresis (CSGE), or DHPLC [Krantz et al, 1998;Yuan et al, 1998Yuan et al, , 2001Crosnier et al, 1999Crosnier et al, , 2000Onouchi et al, 1999;Pilia et al, 1999;Colliton et al, 2001;Heritage et al, 2000Heritage et al, , 2002Giannakudis et al, 2001;Spinner et al, 2001;Stankiewicz et al, 2001;Raas-Rothschild et al, 2002;Röpke et al, 2002;Jurkiewicz et al, 2005]. This screening has largely been performed using scanning techniques such as SSCP analysis, conformation sensitive gel electrophoresis (CSGE), or DHPLC [Krantz et al, 1998;Yuan et al, 1998Yuan et al, , 2001Crosnier et al, 1999Crosnier et al, , 2000Onouchi et al, 1999;Pilia et al, 1999;Colliton et al, 2001;Heritage et al, 2000Heritage et al, , 2002Giannakudis et al, 2001;Spinner et al, 2001;Stankiewicz et al, 2001;Raas-Rothschild et al, 2002;Röpke et al, 2002;Jurkiewicz et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate

et al. 2006

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Alagille syndrome (AGS) is caused by heterozygous mutations in JAG1, and mutations have been previously reported in about 70% of patients who meet clinical diagnostic criteria. We studied a cohort of 247 clinically well-defined patients, and using an aggressive and sequential screening approach we identified JAG1 mutations in 94% of individuals. Mutations were found in 232 out of 247 patients studied and 83 of the mutations were novel. This increase in the mutation rate was accomplished by combining rigorous clinical phenotyping, with a combination of mutation detection techniques, including fluorescence in situ hybridization (FISH), genomic and cDNA sequencing, and quantitative PCR. This higher rate of mutation identification has implications for clinical practice, facilitating genetic counseling, prenatal diagnosis, and evaluation of living-related liver transplant donors. Our results suggest that more aggressive screening may similarly increase the rate of mutation detection in other dominant and recessive disorders.

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Section: Introductionmentioning

confidence: 99%

Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate

et al. 2006

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“…Spondylocostal dysostosis (axial skeleton segmentation disorder) (Bonafe et al, 2003;Bulman et al, 2000;Turnpenny et al, 2003;Whittock et al, 2004) JAG1 Alagille syndrome; patients with JAG1 mutations display variable phenotypes in bile duct paucity, cardiac defects (including tetralogy of Fallot), posterior embryotoxon, spine defects (including butterfly vertebrae) and deafness (Bauer et al, 2010;Colliton et al, 2001;Crosnier et al, 1999;Crosnier et al, 2001;Eldadah et al, 2001;Heritage et al, 2002;Heritage et al, 2000; Krantz et al., 1998; Krantz et al, 1999; Li et al, 1997;Oda et al, 2000;Oda et al, 1997;Raas-Rothschild et al, 2002;Ropke et al, 2003;Stankiewicz et al, 2001;Warthen et al, 2006 DEVELOPMENT…”

Section: Dll3mentioning

confidence: 99%

“…Alagille syndrome; patients with JAG1 mutations display variable phenotypes in bile duct paucity, cardiac defects (including tetralogy of Fallot), posterior embryotoxon, spine defects (including butterfly vertebrae) and deafness (Bauer et al, 2010;Colliton et al, 2001;Crosnier et al, 1999;Crosnier et al, 2001;Eldadah et al, 2001;Heritage et al, 2002;Heritage et al, 2000;Krantz et al, 1998;Krantz et al, 1999;Li et al, 1997;Oda et al, 2000;Oda et al, 1997;Raas-Rothschild et al, 2002;Ropke et al, 2003;Stankiewicz et al, 2001;Warthen et al, 2006) LFNG Spondylocostal dysostosis (axial skeleton segmentation and growth disorder) (Sparrow et al, 2006) MAML2 Mucoepidermoid carcinoma, secondary acute myeloid leukemia (Conkright et al, 2003;Enlund et al, 2004;Tonon et al, 2003) NOTCH1 (Joutel et al, 1997a;Joutel et al, 2004;Joutel et al, 1997b;Oberstein et al, 1999) Skol et al, 2003;Tochigi et al, 2004;Wei and Hemmings, 2000) In addition to the canonical ligands mentioned above, a multitude of non-canonical ligands (reviewed by D'Souza et al, 2010) can activate or inhibit Notch signaling. An interesting example of a non-canonical ligand is Delta-like homolog 1/2 (Dlk1/2), which is structurally similar to the Dll ligands but lacks a DSL domain.…”

Section: Jag1mentioning

confidence: 99%

Notch signaling: simplicity in design, versatility in function

2011

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Notch signaling is evolutionarily conserved and operates in many cell types and at various stages during development. Notch signaling must therefore be able to generate appropriate signaling outputs in a variety of cellular contexts. This need for versatility in Notch signaling is in apparent contrast to the simple molecular design of the core pathway. Here, we review recent studies in nematodes, Drosophila and vertebrate systems that begin to shed light on how versatility in Notch signaling output is generated, how signal strength is modulated, and how cross-talk between the Notch pathway and other intracellular signaling systems, such as the Wnt, hypoxia and BMP pathways, contributes to signaling diversity.Key words: Cis-inhibition, Delta-like, Signaling diversity, Jagged, Notch, Notch intracellular domain Introduction Cells need to sense cues from their extracellular environment and integrate this information into appropriate developmental or physiological responses. Although there are a number of mechanisms that relay information from the exterior of the cell to the interior, a relatively small set of highly evolutionarily conserved signaling pathways stand out as playing particularly crucial roles in this transmission of information. In this roster of 'elite' intracellular signaling mechanisms are the Wnt pathway, the sonic hedgehog (Shh) pathway, the bone morphogenetic protein/transforming growth factor  (BMP/TGF) pathway, phosphatidylinositol 3-kinase/thymoma viral proto-oncogene (PI3K/AKT) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and, the subject of this review, the Notch signaling pathway. Each of these pathways converts information about the concentration of extracellular ligands into specific transcriptional responses in the nucleus. In most cases, the signaling mechanism consists of the 'core' signaling pathway, i.e. the minimal set of protein components required for transducing the signal, and a more elaborate set of 'auxiliary' proteins, which, in various ways, impinge upon the core pathway and modify the signal but are not intrinsically necessary for relaying the signal.Among these highly conserved pathways (Gazave et al., 2009;Richards and Degnan, 2009), the Notch signaling pathway scores highly with regard to simplicity in molecular design, as it contains only a small number of core signaling components (Fig. 1). Despite this, Notch signaling affects cell differentiation decisions not only across a wide spectrum of metazoan species, but also across a broad range of cell types in a single organism and at different steps during cell lineage progression. The pleiotropic actions of Notch in different cell types and organs have recently been reviewed and are summarized in Table 1. In keeping with its important role in many cell types, the mutation of Notch genes leads to diseases in various organs and tissues (Table 2). These studies highlight the fact that the Notch pathway must be able to elicit appropriate responses in many spatially and temporally...

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“…Mutations in the JAG1 can be identified in around 90 % of clinically diagnosed individuals with ALGS (Warthen et al 2006). To date, over 440 different JAG1 gene mutations have been identified in ALGS patients (Li et al 1997; Oda et al 1997; Krantz et al 1998; Yuan et al 1998, 2001; Crosnier et al 1999, 2000; Onouchi et al 1999; Pilia et al 1999; Heritage et al 2000, 2002; Colliton et al 2001; Giannakudis et al 2001; Röpke et al 2003; Jurkiewicz et al 2005; Warthen et al 2006; Kamath et al 2009; Guegan et al 2012; Lin et al 2012; Wang et al 2012). Ten individuals with ALGS features carrying various mutations in the NOTCH2 gene have been reported to date (McDaniell et al 2006; Kamath et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome

et al. 2014

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Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by developmental abnormalities in several organs including the liver, heart, eyes, vertebrae, kidneys, and face. The majority (90-94 %) of ALGS cases are caused by mutations in the JAG1 (JAGGED1) gene, and in a small percent of patients (∼1 %) mutations in the NOTCH2 gene have been described. Both genes are involved in the Notch signaling pathway. To date, over 440 different JAG1 gene mutations and ten NOTCH2 mutations have been identified in ALGS patients. The present study was conducted on a group of 35 Polish ALGS patients and revealed JAG1 gene mutations in 26 of them. Twenty-three different mutations were detected including 13 novel point mutations and six large deletions affecting the JAG1 gene. Review of all mutations identified to date in individuals from Poland allowed us to propose an effective diagnostic strategy based on the mutations identified in the reported patients of Polish descent. However, the distribution of mutations seen in this cohort was not substantively different than the mutation distribution in other reported populations.

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Fifteen novel mutations in theJAGGED1 gene of patients with Alagille syndrome

Cited by 35 publications

References 5 publications

Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate

Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate

Notch signaling: simplicity in design, versatility in function

Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome

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