A Recurrent Mutation in PARK2 Is Associated with Familial Lung Cancer

Slides:

Advertisements

Similar presentations

Previous Estimates of Mitochondrial DNA Mutation Level Variance Did Not Account for Sampling Error: Comparing the mtDNA Genetic Bottleneck in Mice and.

Advertisements

Hereditary Lung Cancer Syndrome Targets Never Smokers with Germline EGFR Gene T790M Mutations Adi Gazdar, MD, Linda Robinson, MS, Dwight Oliver, MD,

Hongda Li, Stephanie L. Bielas, Maha S

High-Throughput Homogeneous Mass Cleave Assay Technology for the Diagnosis of Autosomal Recessive Parkinson's Disease Christopher Schroeder, Michael.

The H Syndrome Is Caused by Mutations in the Nucleoside Transporter hENT3 Vered Molho-Pessach, Israela Lerer, Dvorah Abeliovich, Ziad Agha, Abdulasalam.

Single-Color Digital PCR Provides High-Performance Detection of Cancer Mutations from Circulating DNA Christina Wood-Bouwens, Billy T. Lau, Christine.

DSG2 Mutations Contribute to Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Mark M. Awad, Darshan Dalal, Eunpi Cho, Nuria Amat-Alarcon, Cynthia.

A Novel Mutation and Large Size Polymorphism Affecting the V2 Domain of Keratin 1 in an African-American Family with Severe, Diffuse Palmoplantar Keratoderma.

A Mutation in the Vesicle-Trafficking Protein VAPB Causes Late-Onset Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis Agnes L. Nishimura, Miguel.

Comparison of High-Resolution Melting Analysis, TaqMan Allelic Discrimination Assay, and Sanger Sequencing for Clopidogrel Efficacy Genotyping in Routine.

Total-Genome Analysis of BRCA1/2-Related Invasive Carcinomas of the Breast Identifies Tumor Stroma as Potential Landscaper for Neoplastic Initiation

Exome Sequencing in Brown-Vialetto-Van Laere Syndrome

Identification of a novel mutation in PLA2G6 gene in a Chinese pedigree with familial cortical myoclonic tremor with epilepsy Lehong Gao, Liping Li,

A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa Goranka Tanackovic, Adriana Ransijn,

Familial Deafness, Congenital Heart Defects, and Posterior Embryotoxon Caused by Cysteine Substitution in the First Epidermal-Growth-Factor–Like Domain.

Association of Family History of Specific Cancers With a Younger Age of Onset of Pancreatic Adenocarcinoma Robert R. McWilliams, William R. Bamlet, Kari.

De Novo Loss-of-Function Mutations in SETD5, Encoding a Methyltransferase in a 3p25 Microdeletion Syndrome Critical Region, Cause Intellectual Disability

Shih-Jen Hwang, Guillermina Lozano, Christopher I. Amos, Louise C

Mutations in PADI6 Cause Female Infertility Characterized by Early Embryonic Arrest Yao Xu, Yingli Shi, Jing Fu, Min Yu, Ruizhi Feng, Qing Sang, Bo Liang,

Focused Analysis of Exome Sequencing Data for Rare Germline Mutations in Familial and Sporadic Lung Cancer Yanhong Liu, PhD, Farrah Kheradmand, MD, Caleb.

A Single Recurrent Mutation in the 5′-UTR of IFITM5 Causes Osteogenesis Imperfecta Type V Tae-Joon Cho, Kyung-Eun Lee, Sook-Kyung Lee, Su Jeong Song,

Exome Sequencing Identifies SLC24A5 as a Candidate Gene for Nonsyndromic Oculocutaneous Albinism Ai-Hua Wei, Dong-Jie Zang, Zhe Zhang, Xuan-Zhu Liu,

Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer Lamis Yehia, Farshad.

Dan Doherty, Albert E. Chudley, Gail Coghlan, Gisele E. Ishak, A

De Novo BRCA1 Mutation in a Patient with Breast Cancer and an Inherited BRCA2 Mutation Andrea Tesoriero, Chris Andersen, Melissa Southey, Gino Somers,

Harry R. Hill, Nancy H. Augustine, Robert J. Pryor, Gudrun H

Peter Ianakiev, Michael W

GCM2-Activating Mutations in Familial Isolated Hyperparathyroidism

Haplotype-Sharing Analysis Implicates Chromosome 7q36 Harboring DPP6 in Familial Idiopathic Ventricular Fibrillation Marielle Alders, Tamara T. Koopmann,

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility Tailai Chen, Yuehong Bian, Xiaoman Liu, Shigang Zhao, Keliang.

Secondary Variants in Individuals Undergoing Exome Sequencing: Screening of 572 Individuals Identifies High-Penetrance Mutations in Cancer-Susceptibility.

A Mutation in the Fibroblast Growth Factor 14 Gene Is Associated with Autosomal Dominant Cerebral Ataxia John C. van Swieten, Esther Brusse, Bianca M.

Identification of a Genetic Locus for Ichthyosis Vulgaris on Chromosome 10q22.3– q24.2 Ping Liu, Qingyu Yang, Xu Wang, Aiping Feng, Tao Yang, Rong Yang,

Laurent Gouya Journal of Investigative Dermatology

A Dominantly Inherited 5′ UTR Variant Causing Methylation-Associated Silencing of BRCA1 as a Cause of Breast and Ovarian Cancer D.Gareth R. Evans, Elke.

High Incidence of Later-Onset Fabry Disease Revealed by Newborn Screening* Marco Spada, Severo Pagliardini, Makiko Yasuda, Turgut Tukel, Geetha Thiagarajan,

Mutation of Solute Carrier SLC16A12 Associates with a Syndrome Combining Juvenile Cataract with Microcornea and Renal Glucosuria Barbara Kloeckener-Gruissem,

Simultaneous Amplification, Detection, and Analysis of Common Mutations in the Galactose-1-Phosphate Uridyl Transferase Gene Mohamed Jama, Lesa Nelson,

Mutations in ANKRD11 Cause KBG Syndrome, Characterized by Intellectual Disability, Skeletal Malformations, and Macrodontia Asli Sirmaci, Michail Spiliopoulos,

Autosomal-Dominant Woolly Hair Resulting from Disruption of Keratin 74 (KRT74), a Potential Determinant of Human Hair Texture Yutaka Shimomura, Muhammad.

Exome Sequencing Identifies Autosomal-Dominant SRP72 Mutations Associated with Familial Aplasia and Myelodysplasia Michael Kirwan, Amanda J. Walne, Vincent.

Dominant Mutations in KAT6A Cause Intellectual Disability with Recognizable Syndromic Features Emma Tham, Anna Lindstrand, Avni Santani, Helena Malmgren,

Semidominant Inheritance in Olmsted Syndrome

Exome Sequencing Identifies a DYNC1H1 Mutation in a Large Pedigree with Dominant Axonal Charcot-Marie-Tooth Disease Michael N. Weedon, Robert Hastings,

Biallelic SUN5 Mutations Cause Autosomal-Recessive Acephalic Spermatozoa Syndrome Fuxi Zhu, Fengsong Wang, Xiaoyu Yang, Jingjing Zhang, Huan Wu, Zhou.

Next-Generation Sequencing Identifies Mutations of SMPX, which Encodes the Small Muscle Protein, X-Linked, as a Cause of Progressive Hearing Impairment

A Platform for Rapid Detection of Multiple Oncogenic Mutations With Relevance to Targeted Therapy in Non–Small-Cell Lung Cancer Zengliu Su, Dora Dias-Santagata,

Evidence That the Penetrance of Mutations at the RP11 Locus Causing Dominant Retinitis Pigmentosa Is Influenced by a Gene Linked to the Homologous RP11.

Recurrence of Marfan Syndrome as a Result of Parental Germ-Line Mosaicism for an FBN1 Mutation Terhi Rantamäki, Ilkka Kaitila, Ann-Christine Syvänen,

A Novel and Rapid Method of Determining the Effect of Unclassified MLH1 Genetic Variants on Differential Allelic Expression Sheron Perera, Brian Li,

Autosomal-Dominant Striatal Degeneration Is Caused by a Mutation in the Phosphodiesterase 8B Gene Silke Appenzeller, Anja Schirmacher, Hartmut Halfter,

A Unique Point Mutation in the PMP22 Gene Is Associated with Charcot-Marie-Tooth Disease and Deafness Margaret J. Kovach, Jing-Ping Lin, Simeon Boyadjiev,

Transcriptional Control of SLC26A4 Is Involved in Pendred Syndrome and Nonsyndromic Enlargement of Vestibular Aqueduct (DFNB4) Tao Yang, Hilmar Vidarsson,

Hongda Li, Stephanie L. Bielas, Maha S

Identification of Recurrent Mutations in the ARS (Component B) Gene Encoding SLURP-1 in Two Families with Mal de Meleda Kimberley Morine Ward, Jülide.

Constitutional Mutations of the hSNF5/INI1 Gene Predispose to a Variety of Cancers Nicolas Sévenet, Eammon Sheridan, Daniel Amram, Pascale Schneider,

Oligodontia Is Caused by Mutation in LTBP3, the Gene Encoding Latent TGF-β Binding Protein 3 Abdul Noor, Christian Windpassinger, Irina Vitcu, Marija.

CDKN2A: The IVS2-105A/G Intronic Mutation Found in an Italian Patient Affected by Eight Primary Melanomas Silvia Majore, Caterina Catricalà, Francesco.

Arun Kumar, Satish C. Girimaji, Mahesh R. Duvvari, Susan H. Blanton

Mutations in CHEK2 Associated with Prostate Cancer Risk

Figure 1. Pedigree and clinical picture of the patient

Germline Mutations in CDH23, Encoding Cadherin-Related 23, Are Associated with Both Familial and Sporadic Pituitary Adenomas Qilin Zhang, Cheng Peng,

Mutations in NEXN, a Z-Disc Gene, Are Associated with Hypertrophic Cardiomyopathy Hu Wang, Zhaohui Li, Jizheng Wang, Kai Sun, Qiqiong Cui, Lei Song, Yubao.

Early-Onset Brain Tumor and Lymphoma in MSH2-Deficient Children

Kazuhito Sugimura, Kent D

Mutations in the DLG3 Gene Cause Nonsyndromic X-Linked Mental Retardation Patrick Tarpey, Josep Parnau, Matthew Blow, Hayley Woffendin, Graham Bignell,

Identification and Functional Consequences of a New Mutation (E155G) in the Gene for GCAP1 That Causes Autosomal Dominant Cone Dystrophy Susan E. Wilkie,

Gain-of-Function Mutations in SCN11A Cause Familial Episodic Pain

Identification and Functional Analysis of ZIC3 Mutations in Heterotaxy and Related Congenital Heart Defects Stephanie M. Ware, Jianlan Peng, Lirong Zhu,

A Major Lung Cancer Susceptibility Locus Maps to Chromosome 6q23–25

Presentation transcript:

A Recurrent Mutation in PARK2 Is Associated with Familial Lung Cancer Donghai Xiong, Yian Wang, Elena Kupert, Claire Simpson, Susan M. Pinney, Colette R. Gaba, Diptasri Mandal, Ann G. Schwartz, Ping Yang, Mariza de Andrade, Claudio Pikielny, Jinyoung Byun, Yafang Li, Dwight Stambolian, Margaret R. Spitz, Yanhong Liu, Christopher I. Amos, Joan E. Bailey-Wilson, Marshall Anderson, Ming You The American Journal of Human Genetics Volume 96, Issue 2, Pages 301-308 (February 2015) DOI: 10.1016/j.ajhg.2014.12.016 Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 1 Filtering Strategy in Family A for the Three NSCLC Individuals Subjected to Exome Sequencing The filtering criteria are written on the left side of the workflow. The number of variants that remained after each filtering step is shown in the workflow. The American Journal of Human Genetics 2015 96, 301-308DOI: (10.1016/j.ajhg.2014.12.016) Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 2 Sanger Sequencing Chromatograms of the PARK2 Mutation and the Plot of the Resulting Amino Acid Change in the PARK2 Domain The top panel shows the sequencing chromatograms of the PARK2 germline mutation c.823C>T for the three probands in family A, and the bottom panel presents the schematic plot of PARK2 domains and the amino acid change (p.Arg275Trp) resulting from c.823C>T. Chromatograms of both forward and reverse sequences are given, and the complementary-strand alleles (G>A) are shown. The solid red arrowhead shows the location of the resulting amino acid change in PARK2. The American Journal of Human Genetics 2015 96, 301-308DOI: (10.1016/j.ajhg.2014.12.016) Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 3 The PARK2 c.823C>T (p.Arg275Trp) Mutation in Four Lung-Cancer-Affected Families Basic annotations are as follows: the black filled symbols indicate lung-cancer-affected individuals; an oblique line shows deceased family members; the numbers ending with “ y” under each symbol indicate the age at diagnosis (affected individuals) or last contact (control individuals); “Smk” means a current or former smoker; “Nev” indicates someone who never smoked; “c.823C>T” indicates a subject with the heterozygous c.823C>T (p.Arg275Trp) mutation; and “WT” indicates a subject with wild-type alleles at this locus. In family A, five lung-cancer-affected subjects (III-1, III-4, III-7, III-10, and IV-18 [black filled symbols]; age at onset ranging from 38 to 69 years) without SCLC had the c.823C>T (p.Arg275Trp) mutation. WES was performed for affected individuals III-1, III-4, and IV-18. Subject IV-12 (symbol with vertical black bar in the center) had leukemia. Three individuals (IV-7, IV-9, and V-1 [half-black symbols]) were affected by SCLC. Six unaffected individuals (age at exam ranging from 30 to 55 years) had the c.823C>T (p.Arg275Trp) mutation, and 19 unaffected (age at exam ranging from 26 to 75 years) had wild-type alleles at this locus. In family B, two NSCLC-affected individuals (III-6 and III-7) had the c.823C>T (p.Arg275Trp) mutation. Three unaffected individuals (age at exam ranging from 25 to 49 years) had this mutation, and 13 unaffected (age at exam ranging from 30 to 69 years) had wild-type alleles at this locus. Individual III-4 (symbol with an inner black circle) had both lung cancer and melanoma, but her DNA sample was unavailable for genetic testing. In family C, two NSCLC-affected individuals (II-1 and II-3; ages at onset of 57 and 59 years, respectively) had the c.823C>T (p.Arg275Trp) mutation. Individual I-1 (symbol with an inner black circle) had both lung cancer and prostate cancer, and I-2 (symbol with an inner black circle) had uterine cancer and potentially had lung cancer (this is unverified, and this individual has been out of contact since 2002). In family D, individual II-2 had the mutation (age at onset was 47 years) and had lung adenocarcinoma. Individual I-2 (symbol with an inner black circle) had both lung adenocarcinoma and leukemia. The American Journal of Human Genetics 2015 96, 301-308DOI: (10.1016/j.ajhg.2014.12.016) Copyright © 2015 The American Society of Human Genetics Terms and Conditions