Genetic alterations in the JAG1 gene in Japanese patients with Alagille syndrome

Onouchi, Yoshihiro; Kurahashi, Hiroki; Tajiri, Hitoshi; Ida, Shinobu; Okada, Shintaro; Nakamura, Yusuke

doi:10.1007/s100380050150

Cited by 25 publications

(29 citation statements)

References 12 publications

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“…The prevalence of the facial phenotype in JAG1 -mutation positive individuals is over 90% [Emerick et al 1999] and a similar prevalence has been seen in population-based studies reporting unique JAG1 mutations in Italian, Australian, and Polish populations [Pilia et al, 1999; Heritage et al, 2000, 2002; Ropke et al, 2002; Jurkiewicz et al, 2005]. There have also been reports of ALGS in Asian populations, including Japanese, Korean, and Chinese [Yuan et al, 1998, 2001; Onouchi et al, 1999; Kasahara et al, 2003; Kim et al, 2005; Wang et al, 2008] and all of these described characteristic ALGS facial features, although only one study specifically mentioned confirmation of the facies by a clinical dysmorphologist. In this study we present the results of JAG1 and NOTCH2 mutation analysis of 21 Vietnamese patients with ALGS and a systematic assessment of the agreement among North American dysmorphologists at detecting the presence of ALGS facial features in this population.…”

Section: Introductionmentioning

confidence: 67%

“…Mutations in JAG1 , which is found on chromosome 20, can be identified in over 90% of clinically diagnosed individuals with ALGS [Warthen et al, 2006]. Currently, 377 different JAG1 gene mutations have been identified in ALGS patients [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; Ropke et al, 2002; Jurkiewicz et al, 2005]. More recently, mutations in NOTCH2 were found to cause ALGS and two NOTCH2 mutations have been reported to date [McDaniell et al 2006].…”

Section: Introductionmentioning

confidence: 99%

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Alagille syndrome in a Vietnamese cohort: Mutation analysis and assessment of facial features

Lin

Hoang

Hutchinson

et al. 2012

American J of Med Genetics Pt A

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Alagille syndrome (ALGS, OMIM #118450) is an autosomal dominant disorder that affects multiple organ systems including the liver, heart, eyes, vertebrae, and face. ALGS is caused by mutations in one of two genes in the Notch Signaling Pathway, JAGGED1 or NOTCH2. In this study, analysis of 21 Vietnamese ALGS individuals led to the identification of 19 different mutations (18 JAGGED1 and 1 NOTCH2), 17 of which are novel, including the third reported NOTCH2 mutation in Alagille Syndrome. The spectrum of JAGGED1 mutations in the Vietnamese patients is similar to that previously reported, including nine frameshift, three missense, two splice site, one nonsense, two whole gene, and onw partial gene deletion. The missense mutations are all likely to be disease causing, as two are loss of cysteines (C22R and C78G) and the third creates a cryptic splice site in exon 9 (G386R). No correlation between genotype and phenotype was observed. Assessment of clinical phenotype revealed that skeletal manifestations occur with a higher frequency than in previously reported Alagille cohorts. Facial features were difficult to assess and a Vietnamese pediatric gastroenterologist was only able to identify the facial phenotype in 61% of the cohort. To assess the agreement among North American dysmorphologists at detecting the presence of ALGS facial features in the Vietnamese patients, 37 clinical dysmorphologists evaluated a photographic panel of 20 Vietnamese children with and without ALGS. The dysmorphologists were unable to identify the individuals with ALGS in the majority of cases, suggesting that evaluation of facial features should not be used in the diagnosis of ALGS in this population. This is the first report of mutations and phenotypic spectrum of ALGS in a Vietnamese population.

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Section: Introductionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Alagille syndrome in a Vietnamese cohort: Mutation analysis and assessment of facial features

Lin

Hoang

Hutchinson

et al. 2012

American J of Med Genetics Pt A

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“…The Jagged1 protein consists of several evolutionary conserved domains. These are a signal peptide, the conserved Delta/Serrate/Lag-2 domain (DSL) important for the ligand-receptor interaction, 16 epidermal growth factor (EGF)-like repeats, a cysteine-rich region and a transmembrane domain (Lindsell et al, 1995).So far, 192 different JAG1 mutations in 252 AGS patients have previously been identified (Li et al, 1997;Oda et al, 1997a;Krantz et al, 1998;Crosnier et al, 1999;Pilia et al, 1999, Onouchi et al, 1999 Yuan et al, 1999;Colliton et al, 2000;Crosnier et al, 2000;Heritage et al, 2000;Giannakudis et al, 2001; Yuan et al, 2001; for review see Spinner et al, 2001). Here we present the identification of 36 novel JAG1 mutations in patients with AGS.…”

mentioning

confidence: 91%

“…Sixteen mutations (59%) were de novo and eleven (41%) were transmitted. The mutated allele was in 7 of the inherited mutations of maternal and in 4 of paternal origin.In order to detect a preference for mutations within specific segments of the JAG1 gene causing AGS we analyzed the distribution of 226 different mutations (figure 1), our 36 novel mutations in addition to the 192 different mutations published recently (Li et al, 1997;Oda et al, 1997a;Krantz et al, 1998;Crosnier et al, 1999;Pilia et al, 1999;Onouchi et al, 1999; Yuan et al, 1999;Colliton et al, 2000;Crosnier et al, 2000;Heritage et al, 2000;Giannakudis et al, 2001; Yuan et al, 2001). Mutations occurring in more than one patient were counted only once.…”

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confidence: 99%

Identification of 36 novel Jagged1 (JAG1) mutations in patients with Alagille syndrome

et al. 2002

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Alagille syndrome (AGS) is an autosomal dominant disorder characterized by five major symptoms: cholestasis, vertebral deformity, heart malformations, ocular defects and peculiar facial appearance. The previously described Jagged1 (JAG1) gene on chromosome 20p12 has been identified as being responsible for AGS. JAG1 encodes a transmembrane protein acting as ligand for the evolutionarily conserved Notch signaling pathway. Here we report 36 novel mutations in the JAG1 gene. We identified 12 novel deletions, 4 insertions, 8 missense, 7 nonsense and 5 splice site mutations. All mutations map to the sequence encoding the extracellular part of the Jagged1 protein. The mutations spread over the entire gene with slightly increased rates in exons 2 to 6 and exon 23 and 24. Eight novel missense mutations map to the Delta-Serrate-Lag2 (DSL) domain and adjacent sequences which are important for ligand-receptor interaction. Inheritance was determined in 27 families. Sixteen mutations (55%) were de novo and eleven mutations (45%) were transmitted. Altogether 226 different JAG1 mutations have been described in association with AGS, including our novel 36 mutations. AGS variants are spread over the entire gene with only a few mutations in exon 26. A relatively high number of mutations are clustered in exons 2 to 6. This sequence region shows high interspecies conservation and encodes the Notch receptor-binding region (DSL domain).

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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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Genetic alterations in the JAG1 gene in Japanese patients with Alagille syndrome

Cited by 25 publications

References 12 publications

Alagille syndrome in a Vietnamese cohort: Mutation analysis and assessment of facial features

Alagille syndrome in a Vietnamese cohort: Mutation analysis and assessment of facial features

Identification of 36 novel Jagged1 (JAG1) mutations in patients with Alagille syndrome

Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome

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