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.
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DOI：
10.1002/ajmg.a.35255
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发表时间：
2012-05
影响因子：
2
通讯作者：
Spinner, Nancy B.
中科院分区：
文献类型：
--
作者：
Lin, Henry C.;Phuc Le Hoang;Hutchinson, Anne;Chao, Grace;Gerfen, Jennifer;Loomes, Kathleen M.;Krantz, Ian;Kamath, Binita M.;Spinner, Nancy B.
Alagille综合征（ALGS，OMIM #118450）是一种常染色体显性遗传疾病，影响多个器官系统，包括肝脏，心脏，眼睛，椎骨和面部。ALGS是由Notch信号通路中的两个基因之一JAGGED 1或NOTCH 2突变引起的。在这项研究中，对21名越南ALGS个体的分析导致鉴定出19种不同的突变（18种JAGGED 1和1种NOTCH 2），其中17种是新的，包括第三种报告的Alagille综合征中的NOTCH 2突变。越南患者的JAGGED 1突变谱与以前报道的相似，包括9个移码、3个错义、2个剪接位点、1个无义、2个全基因和1个部分基因缺失。错义突变都可能是致病的，因为两个是半胱氨酸的丢失（C22 R和C78 G），第三个在外显子9中产生了一个隐蔽的剪接位点（G386 R）。基因型和表型之间没有相关性。临床表型的评估显示，骨骼表现发生的频率高于以前报道的Alagille队列。面部特征难以评估，越南儿科胃肠病学家仅能够识别61%队列中的面部表型。为了评估北美畸形学家在检测越南患者ALGS面部特征时的一致性，37名临床畸形学家评估了20名患有和不患有ALGS的越南儿童的摄影小组。在大多数情况下，畸形学家无法识别ALGS的个体，这表明面部特征的评价不应用于诊断该人群中的ALGS。这是第一次报告的突变和表型谱的ALGS在越南人口。
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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影响因子：
3.6
作者：
Krantz, Ian D.;Piccoli, David A.;Spinner, Nancy B.
通讯作者：
Spinner, Nancy B.
影响因子：
30.8
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Spinner, NB
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13.5
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影响因子：
5.1
作者：
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通讯作者：
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