Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis

被引:7
|
作者
Almes, Marion [1 ,2 ,3 ]
Spraul, Anne [2 ,3 ,4 ]
Ruiz, Mathias [5 ]
Girard, Muriel [6 ]
Roquelaure, Bertrand [7 ]
Laborde, Nolwenn [8 ]
Gottrand, Frederic [9 ]
Turquet, Anne [10 ]
Lamireau, Thierry [11 ]
Dabadie, Alain [12 ]
Bonneton, Marjorie [13 ]
Thebaut, Alice [1 ,2 ]
Rohmer, Babara [5 ]
Lacaille, Florence [6 ]
Broue, Pierre [8 ]
Fabre, Alexandre [7 ]
Mention-Mulliez, Karine [9 ]
Bouligand, Jerome [3 ,14 ,15 ]
Jacquemin, Emmanuel [1 ,2 ,3 ]
Gonzales, Emmanuel [1 ,2 ,3 ]
机构
[1] Paris Saclay Univ, Bicetre Hosp,Reference Ctr Biliary Atresia & Gene, Assistance Publ Hop Paris AP HP,ERN RARE LIVER, Pediat Hepatol & Pediat Liver Transplant Unit,FSM, F-94270 Le Kremlin Bicetre, France
[2] Paris Saclay Univ, Hepatinov, INSERM UMR S 1193, F-91400 Orsay, France
[3] AP HP, Plateforme Expertise Malad Rares Paris Saclay, F-94270 Le Kremlin Bicetre, France
[4] Paris Saclay Univ, Bicetre Hosp, AP HP, Biochem Unit,DMU15, F-94270 Le Kremlin Bicetre, France
[5] Bron Hosp, Hepatol & Nutr Unit, Pediat Gastroenterol, F-69677 Lyon, France
[6] Hop Necker Enfants Malad, Hepatol & Nutr Unit, Pediat Gastroenterol, F-75015 Paris, France
[7] Marseille Univ Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-13288 Marseille, France
[8] Toulouse Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-31300 Toulouse, France
[9] Univ Lille, Dept Pediat Gastroenterol Hepatol & Nutr, INSERM U1286, CHU Lille, F-59000 Lille, France
[10] St Denis Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-97405 La Reunion, France
[11] Bordeaux Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-33076 Bordeaux, France
[12] Rennes Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-35033 Rennes, France
[13] Nancy Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-54035 Nancy, France
[14] Paris Saclay Univ, Bicetre Hosp, AP HP, Mol Genet Pharmacol & Hormonol Unit, F-94270 Le Kremlin Bicetre, France
[15] Paris Saclay Univ, Endocrine Physiol & Physiopathol, INSERM UMR 1185, F-94270 Le Kremlin Bicetre, France
关键词
genetic cholestasis; children; NGS; neonatal sclerosing cholangitis; PFIC; Alagille syndrome; transient neonatal cholestasis; NEONATAL CHOLESTASIS; MOLECULAR DIAGNOSIS; GENE-MUTATIONS; DEFICIENCY; VARIANTS; CHILDREN; ASSOCIATION; HEPATOLOGY; DISORDERS; CONSENSUS;
D O I
10.3390/diagnostics12051169
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Cholestasis is a frequent and severe condition during childhood. Genetic cholestatic diseases represent up to 25% of pediatric cholestasis. Molecular analysis by targeted-capture next generation sequencing (NGS) has recently emerged as an efficient diagnostic tool. The objective of this study is to evaluate the use of NGS in children with cholestasis. Methods: Children presenting cholestasis were included between 2015 and 2020. Molecular sequencing was performed by targeted capture of a panel of 34 genes involved in cholestasis and jaundice. Patients were classified into three categories: certain diagnosis; suggested diagnosis (when genotype was consistent with phenotype for conditions without any available OMIM or ORPHANET-number); uncertain diagnosis (when clinical and para-clinical findings were not consistent enough with molecular findings). Results: A certain diagnosis was established in 169 patients among the 602 included (28.1%). Molecular studies led to a suggested diagnosis in 40 patients (6.6%) and to an uncertain diagnosis in 21 patients (3.5%). In 372 children (61.7%), no molecular defect was identified. Conclusions: NGS is a useful diagnostic tool in pediatric cholestasis, providing a certain diagnosis in 28.1% of the patients included in this study. In the remaining patients, especially those with variants of uncertain significance, the imputability of the variants requires further investigations.
引用
收藏
页数:17
相关论文
共 50 条
  • [31] Next-generation Sequencing in the Diagnosis of Metabolic Disease Marked by Pediatric Cataract
    Gillespie, Rachel L.
    Urquhart, Jill
    Anderson, Beverley
    Williams, Simon
    Waller, Sarah
    Ashworth, Jane
    Biswas, Susmito
    Jones, Simon
    Stewart, Fiona
    Lloyd, I. Christopher
    Clayton-Smith, Jill
    Black, Graeme C. M.
    [J]. OPHTHALMOLOGY, 2016, 123 (01) : 217 - 220
  • [32] Molecular Genetic Dissection and Neonatal/Infantile Intrahepatic Cholestasis Using Targeted Next-Generation Sequencing
    Togawa, Takao
    Sugiura, Tokio
    Ito, Koichi
    Endo, Takeshi
    Aoyama, Kohei
    Ohashi, Kei
    Negishi, Yutaka
    Kudo, Toyoichiro
    Ito, Reiko
    Kikuchi, Atsuo
    Arai-Ichinoi, Natsuko
    Kure, Shigeo
    Saitoh, Shinji
    [J]. JOURNAL OF PEDIATRICS, 2016, 171 : 171 - +
  • [33] Diagnostic yield of targeted next-generation sequencing for pediatric hereditary hemolytic anemia
    Choi, Yu Jeong
    Kim, Hongkyung
    Ahn, Won Kee
    Lee, Seung-Tae
    Han, Jung Woo
    Choi, Jong Rak
    Lyu, Chuhl Joo
    Hahn, Seungmin
    Shin, Saeam
    [J]. BMC MEDICAL GENOMICS, 2023, 16 (01)
  • [34] Diagnostic yield of targeted next-generation sequencing for pediatric hereditary hemolytic anemia
    Yu Jeong Choi
    Hongkyung Kim
    Won Kee Ahn
    Seung-Tae Lee
    Jung Woo Han
    Jong Rak Choi
    Chuhl Joo Lyu
    Seungmin Hahn
    Saeam Shin
    [J]. BMC Medical Genomics, 16
  • [35] Next-Generation Sequencing: Targeting Targeted Therapies
    McCutcheon, Justine N.
    Giaccone, Giuseppe
    [J]. CLINICAL CANCER RESEARCH, 2015, 21 (16) : 3584 - 3585
  • [36] Targeted Next-Generation Sequencing for Diagnostics and Forensics
    Minogue, Timothy D.
    Koehler, Jeffrey W.
    Norwood, David A.
    [J]. CLINICAL CHEMISTRY, 2017, 63 (02) : 450 - 452
  • [37] Anchored multiplex FOR for targeted next-generation sequencing
    Zheng, Zongli
    Liebers, Matthew
    Zhelyazkova, Boryana
    Cao, Yi
    Panditi, Divya
    Lynch, Kerry D.
    Chen, Juxiang
    Robinson, Hayley E.
    Shim, Hyo Sup
    Chmielecki, Juliann
    Pao, William
    Engelman, Jeffrey A.
    Iafrate, A. John
    Le, Long Phi
    [J]. NATURE MEDICINE, 2014, 20 (12) : 1479 - 1484
  • [38] Targeted next-generation sequencing in monogenic dyslipidemias
    Hegele, Robert A.
    Ban, Matthew R.
    Cao, Henian
    McIntyre, Adam D.
    Robinson, John F.
    Wang, Jian
    [J]. CURRENT OPINION IN LIPIDOLOGY, 2015, 26 (02) : 103 - 113
  • [39] Importance of targeted next-generation sequencing in pediatric patients with developmental epileptic encephalopathy
    Bari, Savas
    Kirik, Serkan
    Balasar, Ozgur
    [J]. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA, 2023, 69 (10):
  • [40] DNA Sequence Capture and Next-Generation Sequencing for the Molecular Diagnosis of Genetic Cardiomyopathies
    D'Argenio, Valeria
    Frisso, Giulia
    Precone, Vincenza
    Boccia, Angelo
    Fienga, Antonella
    Pacileo, Giuseppe
    Limongelli, Giuseppe
    Paolella, Giovanni
    Calabro, Raffaele
    Salvatore, Francesco
    [J]. JOURNAL OF MOLECULAR DIAGNOSTICS, 2014, 16 (01): : 32 - 44