Analysis of JAG1 gene variant in Chinese patients with Alagille syndrome

Wang, Honglian; Wang, Xiaohong; Li, Qiaoli; Chen, Shiting; Liu, Liyan; Wei, Zengxin; Wang, Lei; Liu, Yun; Zhao, Xinzhi; He, Lin; Wang, Jianshe; Xing, Qinghe

doi:10.1016/j.gene.2012.02.038

Cited by 5 publications

(5 citation statements)

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“…In this cohort, nine missense variants were detected, including six mutations and three SNPs. Among these, c.550C>T, c.766G>T, and c.1156G>A were reported in our previous study [ 14 ]. The de novo mutations c.238A>G and c.2026T>G, as well as c.2071T>A, are novel and predicted to be deleterious; c.2026T>G and c.2071T>A are located in the conserved region of JAG1 .…”

Section: Discussionmentioning

confidence: 83%

“…This study included 91 patients (37 female and 54 male, including 17 reported previously [ 14 ]) from 89 unrelated families referred to the pediatric liver disease clinic of Children’s Hospital of Fudan University between January 2010 and December 2014; cases 30 and 70 were twins, and cases 59 and 69 were brothers.…”

Section: Methodsmentioning

confidence: 99%

“…Approximately 94% of patients with a clinically confirmed diagnosis of ALGS carry JAG1 mutations, of which 60–70% are de novo [ 11 – 13 ]. We previously reported a case series of Chinese ALGS patients with a de novo mutation frequency of 100% (5/5), including an atypical disease case [ 14 ]. To further characterize JAG1 mutations and their origins in Chinese patients with ALGS, we performed a genetic study on a cohort of sporadic patients with at least two of the six major clinical features (chronic cholestasis, cardiac murmur, skeletal abnormalities, ocular abnormalities, a characteristic face, and renal abnormalities).…”

Section: Introductionmentioning

confidence: 99%

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JAG1 Mutation Spectrum and Origin in Chinese Children with Clinical Features of Alagille Syndrome

Dong

Wang

et al. 2015

PLoS ONE

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Alagille syndrome is an autosomal dominant disorder that results from defects in the Notch signaling pathway, which is most frequently due to JAG1 mutations. This study investigated the rate, spectrum, and origin of JAG1 mutations in 91 Chinese children presenting with at least two clinical features of Alagille syndrome (cholestasis, heart murmur, skeletal abnormalities, ocular abnormalities, characteristic facial features, and renal abnormalities). Direct sequencing and/or multiplex-ligation-dependent probe amplification were performed in these patients, and segregation analysis was performed using samples available from the parents. JAG1 disease-causing mutations were detected in 70/91 (76.9%) patients, including 29/70 (41.4%) small deletions, 6/70 (8.6%) small insertions, 16/70 (22.9%) nonsense mutations, 8/70 (11.4%) splice-site mutations, 6/70 (9.4%) missense mutations, and 5/70 (7.1%) gross deletions. Of the mutations detected, 45/62 (72.6%) were novel, and almost all were unique, with the exception of c.439C>T, c.439+1G>A, c.703C>T, c.1382_1383delAC, c.2698C>T, and c.2990C>A, which were detected in two cases each; three cases exhibited entire gene deletions. A majority (69.2%) of the point and frameshift mutations could be detected by the sequencing of eleven exons (exons 3, 5, 6, 11, 14, 16, 18, 21, and 23–25). The mutation detection rate was 50.0% (10/20) in atypical cases that only presented with two or three clinical features of Alagille syndrome. Segregation analysis revealed that 81.1% (30/37) of these mutations were de novo. In conclusion, JAG1 mutations are present in the majority of Chinese pediatric patients with clinical features of Alagille syndrome, and the mutations concentrate on different exons from other reports. Genetic study is important for the diagnosis of atypical Alagille syndrome in Chinese patients.

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Section: Discussionmentioning

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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JAG1 Mutation Spectrum and Origin in Chinese Children with Clinical Features of Alagille Syndrome

Dong

Wang

et al. 2015

PLoS ONE

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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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“…Furthermore, we add NDCG@5 (Normalized Discounted Cumulative Gain) and Recall@100, used in the BEIR benchmark (Thakur et al, 2021b). This combination of metrics lets us estimate our models with a decision support metric such as Recall, binary rankaware metrics such as MRR, and metric with a graded relevance judgment such as NDCG (Wang et al, 2013). For evaluation, we use the BEIR framework 4 that utilizes the Python interface of the TREC evaluation tool (Gysel and de Rijke, 2018).…”

Section: Metricsmentioning

confidence: 99%

Leveraging Domain Adaptation and Data Augmentation to Improve Qur’anic IR in English and Arabic

Pavlova

2023

Proceedings of ArabicNLP 2023

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In this work, we approach the problem of Qur'anic information retrieval (IR) in Arabic and English. Using the latest state-of-the-art methods in neural IR, we research what helps to tackle this task more efficiently. Training retrieval models requires a lot of data, which is difficult to obtain for training in-domain. Therefore, we commence with training on a large amount of general domain data and then continue training on in-domain data. To handle the lack of in-domain data, we employed a data augmentation technique, which considerably improved results in MRR@10 and NDCG@5 metrics, setting the state-of-the-art in Qur'anic IR for both English and Arabic. The absence of an Islamic corpus and domainspecific model for IR task in English motivated us to address this lack of resources and take preliminary steps of the Islamic corpus compilation and domain-specific language model (LM) pre-training, which helped to improve the performance of the retrieval models that use the domain-specific LM as the shared backbone. We examined several language models (LMs) in Arabic to select one that efficiently deals with the Qur'anic IR task. Besides transferring successful experiments from English to Arabic, we conducted additional experiments with retrieval task in Arabic to amortize the scarcity of general domain datasets used to train the retrieval models. Handling Qur'anic IR task combining English and Arabic allowed us to enhance the comparison and share valuable insights across models and languages.

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Analysis of JAG1 gene variant in Chinese patients with Alagille syndrome

Cited by 5 publications

References 16 publications

JAG1 Mutation Spectrum and Origin in Chinese Children with Clinical Features of Alagille Syndrome

JAG1 Mutation Spectrum and Origin in Chinese Children with Clinical Features of Alagille Syndrome

Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome

Leveraging Domain Adaptation and Data Augmentation to Improve Qur’anic IR in English and Arabic

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