The Genomics of Arthrogryposis, a Complex Trait: Candidate Genes and Further Evidence for Oligogenic Inheritance
| Autor: | Maja Hempel, Jennifer E. Posey, Yavuz Bayram, Eric Boerwinkle, Katta M. Girisha, Ender Karaca, Timur Yildirim, Anju Shukla, Jaya Punetha, Ilhan A. Bayhan, Harsha Doddapaneni, Christopher M. Grochowski, Davut Gul, Aysegul Bursali, Davut Pehlivan, Elif Yilmaz Gulec, Richard A. Gibbs, Zeynep Ocak, Jawid M Fatih, Ibrahim Sahin, Gozde Yesil, Burhan Balta, Onur Yildiz, Alper Gezdirici, Tatjana Bierhals, James R. Lupski, Zafer Yüksel, Hatice Mutlu Albayrak, Donna M. Muzny, Jianhong Hu, Fatma Silan, Zeynep Coban Akdemir, Shen Gu, Öztürk Özdemir, Haktan Bağış Erdem, Periyasamy Radhakrishnan, Burcu Tabakci, Beyhan Tüysüz, Nilay Güneş, Shalini N. Jhangiani, Osman Yeşilbaş, Yavuz Sahin, Nursel Elcioglu, Muhsin Elmas, Konstantinos Tsiakas, Sedat Isikay |
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| Přispěvatelé: | Pehlivan, Davut, Bayram, Yavuz, Gunes, Nilay, Akdemir, Zeynep Coban, Shukla, Anju, Bierhals, Tatjana, Tabakci, Burcu, Sahin, Yavuz, Gezdirici, Alper, Fatih, Jawid M., Gulec, Elif Yilmaz, Yesil, Gozde, Punetha, Jaya, Ocak, Zeynep, Grochowski, Christopher M., Karaca, Ender, Albayrak, Hatice Mutlu, Radhakrishnan, Periyasamy, Erdem, Haktan Bagis, Sahin, Ibrahim, Yildirim, Timur, Bayhan, Ilhan A., Bursali, Aysegul, Elmas, Muhsin, Yuksel, Zafer, Ozdemir, Ozturk, Silan, Fatma, Yildiz, Onur, Yesilbas, Osman, Isikay, Sedat, Balta, Burhan, Gu, Shen, Jhangiani, Shalini N., Doddapaneni, Harsha, Hu, Jianhong, Muzny, Donna M., Boerwinkle, Eric, Gibbs, Richard A., Tsiakas, Konstantinos, Hempel, Maja, Girisha, Katta Mohan, Gul, Davut, Posey, Jennifer E., Elcioglu, Nursel H., Tuysuz, Beyhan, Lupski, James R., HKÜ, Sağlık Bilimleri Fakültesi, Fizyoterapi ve Rehabilitasyon Bölümü, YEŞİL, Gözde, İÜC, Cerrahpaşa Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, OMÜ |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Multifactorial Inheritance Candidate gene Vesicular Transport Proteins DE-NOVO DISEASE Cohort Studies MYOPATHY MULTIPLEX CONGENITA SKELETAL-MUSCLE MUTATIONS PATIENT FAT1 MECHANISMS DELETION 0302 clinical medicine Candidate Genes and Further Evidence for Oligogenic Inheritance- AMERICAN JOURNAL OF HUMAN GENETICS cilt.105 ss.132-150 2019 [Pehlivan D. Bayram Y. Gunes N. Akdemir Z. C. Shukla A. Bierhals T. TABAKCI B. Sahin Y. Gezdirici A. Fatih J. M. et al. -The Genomics of Arthrogryposis a Complex Trait] Connectin Copy-number variation Child Genetics (clinical) Exome sequencing Arthrogryposis Genetics Mosaicism Oligogenic Inheritance Genomics Pedigree 3. Good health Child Preschool Female medicine.symptom Adult Genetic Markers Adolescent DNA Copy Number Variations Gestational Age Locus (genetics) Biology Article Young Adult 03 medical and health sciences Exome Sequencing medicine Humans Genetic heterogeneity Infant Newborn Infant Ryanodine Receptor Calcium Release Channel 030104 developmental biology Mutation 030217 neurology & neurosurgery Comparative genomic hybridization |
| Zdroj: | The American Journal of Human Genetics |
| Popis: | Erdem, Haktan Bagis/0000-0002-4391-1387; Albayrak, Hatice Mutlu/0000-0001-5624-3878; isikay, sedat/0000-0003-0103-9612; Grochowski, Christopher/0000-0002-3884-7720; Gezdirici, Alper/0000-0002-2432-9279; KM, Girisha/0000-0002-0139-8239; Gu, Shen/0000-0003-3107-1218; YESIL, GOZDE/0000-0003-1964-6306; Gezdirici, Alper/0000-0002-2432-9279; Tuysuz, Beyhan/0000-0002-9620-5021; Fatih, Jawid/0000-0002-3927-2711; YUKSEL, Zafer/0000-0002-2085-5773; Balta, Burhan/0000-0003-2672-2493; Posey, Jennifer/0000-0003-4814-6765; Bayhan, Ilhan/0000-0001-8308-1309; Punetha, Jaya/0000-0002-6774-4464; YILDIRIM, Timur/0000-0003-0291-7632 WOS:000473723000011 PubMed ID: 31230720 Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohort of 89 families with the clinical sign of arthrogryposis. Additional molecular techniques including array comparative genomic hybridization (aCGH) and Droplet Digital PCR (ddPCR) were performed on individuals who were found to have pathogenic copy number variants (CNVs) and mosaicism, respectively. A molecular diagnosis was established in 65.2% (58/89) of families. Eleven out of 58 families (19.0%) showed evidence for potential involvement of pathogenic variation at more than one locus, probably driven by absence of heterozygosity (AOH) burden due to identity-by-descent (IBD). RYR3, MYOM2, ERGIC1, SPTBN4, and ABCA7 represent genes, identified in two or more families, for which mutations are probably causative for arthrogryposis. We also provide evidence for the involvement of CNVs in the etiology of arthrogryposis and for the idea that both mono-allelic and bi-allelic variants in the same gene cause either similar or distinct syndromes. We were able to identify the molecular etiology in nine out of 20 families who underwent reanalysis. In summary, our data from family-based ES further delineate the molecular etiology of arthrogryposis, yielded several candidate disease-associated genes, and provide evidence for mutational burden in a biological pathway or network. Our study also highlights the importance of reanalysis of individuals with unsolved diagnoses in conjunction with sequencing extended family members. National Human Genome Research Institute (NHGRI)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [UM1 HG006542]; National Heart, Lung, and Blood Institute (NHLBI)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [UM1 HG006542]; NHGRIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [K08 HG008986]; National Institutes of Health - Brain Disorders and Development Training Grant [T32 NS043124-17]; Clinical Research Training Scholarship in Neuromuscular Disease; Tubitak project, TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [217S675]; Indian Council of Medical Research, New Delhi, IndiaIndian Council of Medical Research (ICMR) [5/13/58/2015/NCD-III]; [R35 NS105078]; [512848]; NATIONAL HUMAN GENOME RESEARCH INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [K08HG008986, UM1HG006542, K08HG008986, UM1HG006542, UM1HG006542, UM1HG006542, K08HG008986, UM1HG006542] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R35NS105078, T32NS043124, T32NS043124, T32NS043124, R35NS105078, T32NS043124, T32NS043124, R35NS105078, T32NS043124, T32NS043124, T32NS043124, R35NS105078] Funding Source: NIH RePORTER This work was supported in part by R35 NS105078 and MDA#512848 to J.R.L. and a jointly funded National Human Genome Research Institute (NHGRI) and National Heart, Lung, and Blood Institute (NHLBI) grant to the Baylor-Hopkins Center for Mendelian Genomics (UM1 HG006542). J.E.P. is supported by NHGRI K08 HG008986. D.P. is supported by the National Institutes of Health - Brain Disorders and Development Training Grant (T32 NS043124-17) and a Clinical Research Training Scholarship in Neuromuscular Disease partnered by the American Brain Foundation (ABF) and Muscle Study Group (MSG). This study is partly funded by Tubitak project number 217S675, Turkey to N.E. and B.T.. This study is partly funded by Indian Council of Medical Research, New Delhi, India with File no.: No. 5/13/58/2015/NCD-III to A.S. |
| Databáze: | OpenAIRE |
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