Clinical utility gene card for: Progressive familial intrahepatic cholestasis type 1

Gonzalès, Emmanuel; Spraul, Anne; Jacquemin, Emmanuel

doi:10.1038/ejhg.2013.186

Cited by 10 publications

(7 citation statements)

References 21 publications

(30 reference statements)

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“…Table S16) despite it having not been previously associated with any type of cancer. A variant with a deleterious effect on ATP8B1 may lead to ATP8B1 ‐related diseases, such as progressive familial intrahepatic cholestasis [Gonzales et al., ], but should not increase the chances of developing BC. Thus, while our framework may be effective at prioritizing variants, only genes with previous association to a disease should be included in analyses similar to the present study to minimize falsely prioritized variants.…”

Section: Discussionmentioning

confidence: 99%

“…Initially, it was included in the list of prioritized HBOC genes provided by ENIGMA, but evidence for its association with HBOC is lacking in the published literature. Furthermore, it is not a known susceptibility gene for any type of cancer (mutations in ATP8B1 cause progressive familial intrahepatic cholestasis [Gonzales et al., ]) and is infrequently mutated in breast tumors in several studies (e.g., see Cancer Genome Atlas Network [2012]).…”

Section: Methodsmentioning

confidence: 99%

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Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking KnownBRCAMutations

et al. 2016

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BRCA1 and BRCA2 testing for hereditary breast and ovarian cancer (HBOC) does not identify all pathogenic variants. Sequencing of 20 complete genes in HBOC patients with uninformative test results (N = 287), including noncoding and flanking sequences of ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51B, STK11, TP53, and XRCC2, identified 38,372 unique variants. We apply information theory (IT) to predict and prioritize noncoding variants of uncertain significance in regulatory, coding, and intronic regions based on changes in binding sites in these genes. Besides mRNA splicing, IT provides a common framework to evaluate potential affinity changes in transcription factor (TFBSs), splicing regulatory (SRBSs), and RNA-binding protein (RBBSs) binding sites following mutation. We prioritized variants affecting the strengths of 10 splice sites (four natural, six cryptic), 148 SRBS, 36 TFBS, and 31 RBBS. Three variants were also prioritized based on their predicted effects on mRNA secondary (2°) structure and 17 for pseudoexon activation. Additionally, four frameshift, two in-frame deletions, and five stop-gain mutations were identified. When combined with pedigree information, complete gene sequence analysis can focus attention on a limited set of variants in a wide spectrum of functional mutation types for downstream functional and co-segregation analysis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking KnownBRCAMutations

et al. 2016

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“…About 80 and 100 genetic mutations have been identified in PFIC1 and PFIC2 patients, respectively [17,18]. Despite PFICs being autosomal recessive hereditary diseases, compound heterozygous or homozygous mutations may be associated with structural and functional defects.…”

Section: Discussionmentioning

confidence: 99%

Progressive Familial Intrahepatic Cholestasis in Korea: A Clinicopathological Study of Five Patients

Kang

Hong

et al. 2019

J Pathol Transl Med

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Background Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive liver diseases that present as neonatal cholestasis. Little is known of this disease in Korea. Methods The records of five patients histologically diagnosed with PFIC, one with PFIC1 and four with PFIC2, by liver biopsy or transplant were reviewed, and ATP8B1 and ABCB11 mutation status was analyzed by direct DNA sequencing. Clinicopathological characteristics were correlated with genetic mutations. Results The first symptom in all patients was jaundice. Histologically, lobular cholestasis with bile plugs was the main finding in all patients, whereas diffuse or periportal cholestasis was identified only in patients with PFIC2. Giant cells and ballooning of hepatocytes were observed in three and three patients with PFIC2, respectively, but not in the patient with PFIC1. Immunostaining showed total loss of bile salt export pump in two patients with PFIC2 and focal loss in two. Lobular and portal based fibrosis were more advanced in PFIC2 than in PFIC1. ATP8B1 and ABCB11 mutations were identified in one PFIC1 and two PFIC2 patients, respectively. One PFIC1 and three PFIC2 patients underwent liver transplantation (LT). At age 7 months, one PFIC2 patient was diagnosed with concurrent hepatocellular carcinoma and infantile hemangioma in an explanted liver. The patient with PFIC1 developed steatohepatitis after LT. One patient showed recurrence of PFIC2 after 10 years and underwent LT. Conclusions PFIC is not rare in patients with neonatal cholestasis of unknown origin. Proper clinicopathologic correlation and genetic testing can enable early detection and management.

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“…Insertion, deletion, nonsense, and splicing mutations of the implicated genes result in damaging effects. Detection of biallelic mutations is accepted as diagnostic [17,18,19].…”

Section: Mutational Analysismentioning

confidence: 99%

Progressive familial intrahepatic cholestasis in children

Sevinç¹,

Ağın²,

Doğan³

2018

Ann Gastroenterol Dig Syst

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Clinical utility gene card for: Progressive familial intrahepatic cholestasis type 1

Cited by 10 publications

References 21 publications

Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking KnownBRCAMutations

Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking KnownBRCAMutations

Progressive Familial Intrahepatic Cholestasis in Korea: A Clinicopathological Study of Five Patients

Progressive familial intrahepatic cholestasis in children

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