Whole genome sequencing in families with oligodontia

被引:1
|
作者
Mitscherling, Janna [1 ,2 ]
Sczakiel, Henrike L. [3 ,4 ,5 ,6 ]
Kiskemper-Nestorjuk, Olga [1 ,2 ]
Winterhalter, Sibylle [4 ,7 ]
Mundlos, Stefan [3 ,4 ,6 ]
Bartzela, Theodosia [1 ,2 ,8 ]
Mensah, Martin A. [3 ,4 ,6 ,9 ]
机构
[1] Charite Univ Med Berlin, Freie Univ Berlin, Humboldt Univ Berlin, Dept Orthodont & Dentofacial Orthoped,Charite Ctr, 2lnstitute Biometry & Clin Epidemiol, Berlin, Germany
[2] Berlin Inst Hlth, Berlin, Germany
[3] Charite Univ Med Berlin, Freie Univ Berlin, Inst Med Genet & Human Genet, Augustenburger Pl 1, D-13353 Berlin, Germany
[4] Humboldt Univ, Augustenburger Pl 1, D-13353 Berlin, Germany
[5] Charite Univ Med Berlin, Berlin Inst Hlth, BIH Biomed Innovat Acad, Jr Clinician Scientist Program, Berlin, Germany
[6] Max Planck Inst Mol Genet, RG Dev & Dis, Berlin, Germany
[7] Charite Univ Med Berlin, Freie Univ Berlin, Dept Ophthalmol, Berlin, Germany
[8] Tech Univ Dresden, Dept Orthodont, Dresden, Germany
[9] Charite Univ Med Berlin, Berlin Inst Hlth, BIH Biomed Innovat Acad, Digital Clinician Scientist Program, Berlin, Germany
关键词
genetics; genomics; growth/development; molecular genetics; oligodontia; tooth development; JOINT CONSENSUS RECOMMENDATION; OF-FUNCTION MUTATIONS; COPY-NUMBER VARIANTS; TOOTH AGENESIS; INHERITED ANOMALIES; MEDICAL GENETICS; AMERICAN-COLLEGE; STANDARDS; PAX9;
D O I
10.1111/odi.14816
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
Background/ObjectivesTooth agenesis (TA) is among the most common malformations in humans. Although several causative mutations have been described, the genetic cause often remains elusive. Here, we test whether whole genome sequencing (WGS) could bridge this diagnostic gap.MethodsIn four families with TA, we assessed the dental phenotype using the Tooth Agenesis Code after intraoral examination and radiographic and photographic documentation. We performed WGS of index patients and subsequent segregation analysis.ResultsWe identified two variants of uncertain significance (a potential splice variant in PTH1R, and a 2.1 kb deletion abrogating a non-coding element in FGF7) and three pathogenic variants: a novel frameshift in the final exon of PITX2, a novel deletion in PAX9, and a known nonsense variant in WNT10A. Notably, the FGF7 variant was found in the patient, also featuring the WNT10A variant. While mutations in PITX2 are known to cause Axenfeld-Rieger syndrome 1 (ARS1) predominantly featuring ocular findings, accompanied by dental malformations, we found the PITX2 frameshift in a family with predominantly dental and varying ocular findings.ConclusionSevere TA predicts a genetic cause identifiable by WGS. Final exon PITX2 frameshifts can cause a predominantly dental form of ARS1.
引用
收藏
页码:3935 / 3950
页数:16
相关论文
共 50 条
  • [31] Whole genome sequencing - A challenge for genome diagnostics ["Whole genome sequencing" - Eine herausforderung für die genomdiagnostik]
    Streubel B.
    Der Gynäkologe, 2014, 47 (8): : 565 - 567
  • [32] WHOLE GENE, WHOLE HAPLOTYPE AND WHOLE GENOME SEQUENCING IN HUMAN
    Cereb, Nezih
    Kim, HwaRan
    Lee, Jeongll
    Yang, Soo Young
    HUMAN IMMUNOLOGY, 2017, 78 : 130 - 130
  • [33] A pipeline for sample tagging of whole genome bisulfite sequencing data using genotypes of whole genome sequencing
    Zhe Xu
    Si Cheng
    Xin Qiu
    Xiaoqi Wang
    Qiuwen Hu
    Yanfeng Shi
    Yang Liu
    Jinxi Lin
    Jichao Tian
    Yongfei Peng
    Yong Jiang
    Yadong Yang
    Jianwei Ye
    Yilong Wang
    Xia Meng
    Zixiao Li
    Hao Li
    Yongjun Wang
    BMC Genomics, 24
  • [34] A pipeline for sample tagging of whole genome bisulfite sequencing data using genotypes of whole genome sequencing
    Xu, Zhe
    Cheng, Si
    Qiu, Xin
    Wang, Xiaoqi
    Hu, Qiuwen
    Shi, Yanfeng
    Liu, Yang
    Lin, Jinxi
    Tian, Jichao
    Peng, Yongfei
    Jiang, Yong
    Yang, Yadong
    Ye, Jianwei
    Wang, Yilong
    Meng, Xia
    Li, Zixiao
    Li, Hao
    Wang, Yongjun
    BMC GENOMICS, 2023, 24 (01)
  • [35] Diagnostic and clinical utility of whole genome sequencing in a cohort of undiagnosed Chinese families with rare diseases
    Hong-Yan Liu
    Liyuan Zhou
    Meng-Yue Zheng
    Jia Huang
    Shu Wan
    Aiying Zhu
    Mingjie Zhang
    Anliang Dong
    Ling Hou
    Jia Li
    Haiming Xu
    Bingjian Lu
    Weiguo Lu
    Pengyuan Liu
    Yan Lu
    Scientific Reports, 9
  • [36] Whole genome sequencing in African-American families identifies candidate genes for myopia risk
    Mahmoodi, Evanjelin
    Musolf, Anthony
    Ciner, Elise
    Bailey-Wilson, Joan
    Stambolian, Dwight
    EUROPEAN JOURNAL OF HUMAN GENETICS, 2023, 31 : 341 - 341
  • [37] De novo mutations discovered in 8 Mexican American families through whole genome sequencing
    Heming Wang
    Xiaofeng Zhu
    BMC Proceedings, 8 (Suppl 1)
  • [38] Diagnostic and clinical utility of whole genome sequencing in a cohort of undiagnosed Chinese families with rare diseases
    Liu, Hong-Yan
    Thou, Liyuan
    Zheng, Meng-Yue
    Huang, Jia
    Wan, Shu
    Zhu, Aiying
    Zhang, Mingjie
    Dong, Anliang
    Hou, Ling
    Li, Jia
    Xu, Haiming
    Lu, Bingjian
    Lu, Weiguo
    Liu, Pengyuan
    Lu, Yan
    SCIENTIFIC REPORTS, 2019, 9 (1)
  • [39] Whole genome sequencing of Caribbean Hispanic families with late-onset Alzheimer's disease
    Vardarajan, Badri N.
    Barral, Sandra
    Jaworski, James
    Beecham, Gary W.
    Blue, Elizabeth
    Tosto, Giuseppe
    Reyes-Dumeyer, Dolly
    Medrano, Martin
    Lantigua, Rafael
    Naj, Adam
    Thornton, Timothy
    DeStefano, Anita
    Martin, Eden
    Wang, Li-San
    Brown, Lisa
    Bush, William
    van Duijn, Cornelia
    Goate, Allison
    Farrer, Lindsay
    Haines, Jonathan L.
    Boerwinkle, Eric
    Schellenberg, Gerard
    Wijsman, Ellen
    Pericak-Vance, Margaret A.
    Mayeux, Richard
    ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 2018, 5 (04): : 406 - 417
  • [40] WHOLE GENOME SEQUENCING OF MULTIPLY AFFECTED SCHIZOPHRENIA AND BIPOLAR DISORDER FAMILIES FROM THE AZORES AND MADEIRA
    Bigdeli, T. Bernard
    Kelly, Benke
    Maher, Brion
    Knowles, James
    Medeiros, Helena
    Sobell, Janet
    Bevilacqua, Elizabeth
    Moran, Jennifer
    Nemesh, J.
    Genovese, Giulio
    Handsaker, Robert
    O'Dushlaine, Colm
    Pato, Michele
    McCarroll, Steven
    Pato, Carlos
    Fanous, Ayman
    EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2017, 27 : S192 - S192