6 results on '"CHROMOSOME 16P11.2"'
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2. Coronin-1A: immune deficiency in humans and mice
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Divya Punwani, Jason Yu, Barry J. Pelz, Jennifer M. Puck, Karly Kondratowicz, Melanie M. Makhija, Nicoleta C. Arva, and Kristian T. Schafernak
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medicine.drug_class ,T cell ,Knockout ,Immunology ,Autoimmunity ,Disease ,Biology ,Chromosome 16p11.2 ,Monoclonal antibody ,medicine.disease_cause ,primary immunodeficiency ,Article ,Autoimmune Diseases ,Mice ,Immune system ,immune dysregulation ,thymus ,medicine ,Immunology and Allergy ,Animals ,Humans ,combined immunodeficiency ,Protein Interaction Domains and Motifs ,Molecular Targeted Therapy ,epstein-barr virus (EBV) ,B cell ,Genetic Association Studies ,Mice, Knockout ,Leukemia ,epstein-barr virus ,Animal ,Microfilament Proteins ,Immunologic Deficiency Syndromes ,combined immunodeficiency (CID) ,Immune dysregulation ,medicine.disease ,Disease Models, Animal ,medicine.anatomical_structure ,Phenotype ,Disease Models ,Mutation ,Primary immunodeficiency ,Carrier Proteins ,Protein Binding - Abstract
Since the discovery of coronins in 1991 significant research has been carried out to understand their molecular structure and cellular mechanisms of the action. While a number of binding partners have been discovered, the precise mechanisms of action of Coronin-1A are still being elucidated, both in vitro and in vivo. The role of Coronin-1A in the development and function of the immune system is irrefutable, in both humans and mice, and deficiency of Coronin-1A results in CID. Although some immunological manifestations of Coronin-1A deficiency differed between the patients described so far, absence of Coronin-1A affected the T cell compartment in all patients. B cell numbers were lower than normal and antibody responses were impaired. Variable NK cell defects associated with absent Coronin-1A to date will require detailed analysis of further patients. HCT was curative for patients with Coronin-1A deficiency when the disease was diagnosed early, before onset of irreversible complications arising from infections and EBV associated malignancy. With new evidence about the potential of anti-Coronin-1A monoclonal antibodies to treat B cell malignancies and T cell-mediated auto-inflammatory diseases, Coronin-1A can now be said to be involved in the overall regulation of the immune system, and inappropriate expression can lead to either immune deficiency or autoimmunity.
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- 2015
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3. Familial Juvenile Hyperuricemic Nephropathy: Localization of the Gene on Chromosome 16p11.2—and Evidence for Genetic Heterogeneity
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Ivan Sebesta, Blanka Stibůrková, Stanislav Kmoch, Jurg Ott, Jacek Majewski, and Wenyong Zhang
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Adult ,Male ,Thyroid Hormones ,Adolescent ,Gout ,Penetrance ,Locus (genetics) ,Chromosome 16p11.2 ,Biology ,Medullary cystic kidney disease ,Renal disease ,Genetic Heterogeneity ,Mucoproteins ,Genetic linkage ,Genetic heterogeneity, FJHN ,Uromodulin ,Genetics ,medicine ,Humans ,Genetics(clinical) ,Crossing Over, Genetic ,Renal Insufficiency ,Age of Onset ,Child ,Genetics (clinical) ,Czech Republic ,Genes, Dominant ,Familial juvenile hyperuricemic nephropathy ,Genetic heterogeneity ,Haplotype ,Chromosome Mapping ,Membrane Proteins ,Middle Aged ,medicine.disease ,Pedigree ,Uric Acid ,Haplotypes ,Female ,Lod Score ,Age of onset ,Carrier Proteins ,Chromosomes, Human, Pair 16 ,Research Article - Abstract
Familial juvenile hyperuricemic nephropathy (FJHN), is an autosomal dominant renal disease characterized by juvenile onset of hyperuricemia, gouty arthritis, and progressive renal failure at an early age. Using a genomewide linkage analysis in three Czech affected families, we have identified, on chromosome 16p11.2, a locus for FJHN and have found evidence for genetic heterogeneity and reduced penetrance of the disease. The maximum two-point LOD score calculated with allowance for heterogeneity (HLOD) was 4.70, obtained at recombination fraction 0, with marker D16S3036; multipoint linkage analysis yielded a maximum HLOD score of 4.76 at the same location. Haplotype analysis defined a 10-cM candidate region between flanking markers D16S501 and D16S3113, exhibiting crossover events with the disease locus. The candidate interval contains several genes expressed in the kidney, two of which—uromodulin and NADP-regulated thyroid-hormone–binding protein—represent promising candidates for further analysis.
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- 2000
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4. Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity
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D. L. Cousminer, D. J. Berry, N. J. Timpson, W. Ang, E. Thiering, E. M. Byrne, H. R. Taal, V. Huikari, J. P. Bradfield, M. Kerkhof, M. M. Groen Blokhuis, E. Kreiner Moller, M. Marinelli, C. Holst, J. T. Leinonen, J. R. B. Perry, I. Surakka, O. Pietilainen, J. Kettunen, V. Anttila, M. Kaakinen, U. Sovio, A. Pouta, S. Das, V. Lagou, C. Power, I. Prokopenko, D. M. Evans, J. P. Kemp, B. St Pourcain, S. Ring, A. Palotie, E. Kajantie, C. Osmond, T. Lehtimaki, J. S. Viikari, M. Kahonen, N. M. Warrington, S. J. Lye, L. J. Palmer, C. M. T. Tiesler, C. Flexeder, G. W. Montgomery, S. E. Medland, A. Hofman, H. Hakonarson, M. Guxens, M. Bartels, V. Salomaa, J. M. Murabito, J. Kaprio, T. I. A. Sorensen, F. Ballester, H. Bisgaard, D. I. Boomsma, G. H. Koppelman, S. F. A. Grant, V. W. V. Jaddoe, N. G. Martin, J. Heinrich, C. E. Pennell, O. T. Raitakari, J. G. Eriksson, G. D. Smith, E. Hypponen, M. R. Jarvelin, M. I. McCarthy, S. Ripatti, E. Widen, Adair LS, Ang W, Atalay M, van Beijsterveldt T, Bergen N, Benke K, Berry DJ, Boomsma DI, Bradfield JP, Charoen P, Coin L, Cooper C, Cousminer DL, Das S, Davis OS, Dedoussis GV, Elliott P, Estivill X, Evans DM, Feenstra B, Flexeder C, Frayling T, Freathy RM, Gaillard R, Geller F, Gillman M, Grant SF, Groen Blokhuis M, Goh LK, Guxens M, Hakonarson H, Hattersley AT, Haworth CM, Hadley D, Hedebrand J, Heinrich J, Hinney A, Hirschhorn JN, Hocher B, Holloway JW, Holst C, Hottenga JJ, Horikoshi M, Huikari V, Hypponen E, Iñiguez C, Jaddoe VW, Jarvelin MR, Kaakinen M, Kilpeläinen TO, Kirin M, Kowgier M, Lakka HM, Lakka TA, Lange LA, Lawlor DA, Lehtimäki T, Lewin A, Lindgren C, Lindi V, Maggi R, Marsh J, McCarthy MI, Melbye M, Middeldorp C, Millwood I, Mohlke KL, Mook Kanamori DO, Murray JC, Nivard M, Nohr EA, Ntalla I, Oken E, Ong KK, O'Reilly PF, Palmer LJ, Panoutsopoulou K, Pararajasingham J, Pearson ER, Pennell CE, Power C, Price TS, Prokopenko I, Raitakari OT, Rodriguez A, Salem RM, Saw SM, Scherag A, Sebert S, Siitonen N, Simell O, Sørensen TI, Sovio U, Pourcain BS, Strachan DP, Sunyer J, Taal HR, Teo YY, Thiering E, Tiesler C, Timpson NJ, Uitterlinden AG, Valcárcel B, Warrington NM, White S, Widén E, Willemsen G, Wilson JF, Yaghootkar H, Zeggini E, Elks CE, Perry JR, Sulem P, Chasman DI, Franceschini N, He C, Lunetta KL, Visser JA, Byrne EM, Gudbjartsson DF, Esko T, Koller DL, Kutalik Z, Lin P, Mangino M, Marongiu M, McArdle PF, Smith AV, Stolk L, van Wingerden SH, Zhao JH, Albrecht E, Corre T, Ingelsson E, Hayward C, Magnusson PK, Smith EN, Ulivi S, Warrington M, Zgaga L, Alavere H, Amin N, Aspelund T, Bandinelli S, Barroso I, Berenson GS, Bergmann S, Blackburn H, Boerwinkle E, Buring JE, Busonero F, Campbell H, Chanock SJ, Chen W, Cornelis MC, Couper D, Coviello AD, de Faire U, de Geus EJ, Deloukas P, Döring A, Davey Smith G, Easton DF, Eiriksdottir G, Emilsson V, Eriksson J, Ferrucci L, Folsom AR, Foroud T, Garcia M, GASPARINI, PAOLO, Gieger C, Gudnason V, Hall P, Hankinson SE, Ferreli L, Heath AC, Hernandez DG, Hofman A, Hu FB, Illig T, Järvelin MR, Johnson AD, Karasik D, Khaw KT, Kiel DP, Kolcic I, Kraft P, Launer LJ, Laven JS, Li S, Liu J, Levy D, Martin NG, McArdle WL, Mooser V, Murray SS, Nalls MA, Navarro P, Nelis M, Ness AR, Northstone K, Oostra BA, Peacock M, Palotie A, Paré G, Parker AN, Pedersen NL, Peltonen L, Pharoah P, Polasek O, Plump AS, Pouta A, Porcu E, Rafnar T, Rice JP, Ring SM, Rivadeneira F, Rudan I, Sala C, Salomaa V, Sanna S, Schlessinger D, Schork NJ, Scuteri A, Segrè AV, Shuldiner AR, Soranzo N, Srinivasan SR, Tammesoo ML, Tikkanen E, Toniolo D, Tsui K, Tryggvadottir L, Tyrer J, Uda M, van Dam RM, van Meurs JB, Vollenweider P, Waeber G, Wareham NJ, Waterworth DM, Weedon MN, Wichmann HE, Wright AF, Young L, Zhai G, Zhuang WV, Bierut LJ, Boyd HA, Crisponi L, Demerath EW, van Duijn CM, Econs MJ, Harris TB, Hunter DJ, Loos RJ, Metspalu A, Montgomery GW, Ridker PM, Spector TD, Streeten EA, Stefansson K, Thorsteinsdottir U, Widen E, Murabito JM, Murray A., D'ADAMO, ADAMO PIO, Cousminer, Diana L, Berry, Diane J, Timpson, Nicholas J, Ang, Wei, Hyppönen, Elina, Widen, Elisabéth, ReproGen Consortium, Early Growth Genetics (EGG) Consortium, Pediatrics, Epidemiology, Internal Medicine, D. L., Cousminer, D. J., Berry, N. J., Timpson, W., Ang, E., Thiering, E. M., Byrne, H. R., Taal, V., Huikari, J. P., Bradfield, M., Kerkhof, M. M., Groen Blokhui, E., Kreiner Moller, M., Marinelli, C., Holst, J. T., Leinonen, J. R. B., Perry, I., Surakka, O., Pietilainen, J., Kettunen, V., Anttila, M., Kaakinen, U., Sovio, A., Pouta, S., Da, V., Lagou, C., Power, I., Prokopenko, D. M., Evan, J. P., Kemp, B., St Pourcain, S., Ring, A., Palotie, E., Kajantie, C., Osmond, T., Lehtimaki, J. S., Viikari, M., Kahonen, N. M., Warrington, S. J., Lye, L. J., Palmer, C. M. T., Tiesler, C., Flexeder, G. W., Montgomery, S. E., Medland, A., Hofman, H., Hakonarson, M., Guxen, M., Bartel, V., Salomaa, J. M., Murabito, J., Kaprio, T. I. A., Sorensen, F., Ballester, H., Bisgaard, D. I., Boomsma, G. H., Koppelman, S. F. A., Grant, V. W. V., Jaddoe, N. G., Martin, J., Heinrich, C. E., Pennell, O. T., Raitakari, J. G., Eriksson, G. D., Smith, E., Hypponen, M. R., Jarvelin, M. I., Mccarthy, S., Ripatti, E., Widen, Adair, L, Ang, W, Atalay, M, van Beijsterveldt, T, Bergen, N, Benke, K, Berry, Dj, Boomsma, Di, Bradfield, Jp, Charoen, P, Coin, L, Cooper, C, Cousminer, Dl, Das, S, Davis, O, Dedoussis, Gv, Elliott, P, Estivill, X, Evans, Dm, Feenstra, B, Flexeder, C, Frayling, T, Freathy, Rm, Gaillard, R, Geller, F, Gillman, M, Grant, Sf, Groen Blokhuis, M, Goh, Lk, Guxens, M, Hakonarson, H, Hattersley, At, Haworth, Cm, Hadley, D, Hedebrand, J, Heinrich, J, Hinney, A, Hirschhorn, Jn, Hocher, B, Holloway, Jw, Holst, C, Hottenga, Jj, Horikoshi, M, Huikari, V, Hypponen, E, Iñiguez, C, Jaddoe, Vw, Jarvelin, Mr, Kaakinen, M, Kilpeläinen, To, Kirin, M, Kowgier, M, Lakka, Hm, Lakka, Ta, Lange, La, Lawlor, Da, Lehtimäki, T, Lewin, A, Lindgren, C, Lindi, V, Maggi, R, Marsh, J, Mccarthy, Mi, Melbye, M, Middeldorp, C, Millwood, I, Mohlke, Kl, Mook Kanamori, Do, Murray, Jc, Nivard, M, Nohr, Ea, Ntalla, I, Oken, E, Ong, Kk, O'Reilly, Pf, Palmer, Lj, Panoutsopoulou, K, Pararajasingham, J, Pearson, Er, Pennell, Ce, Power, C, Price, T, Prokopenko, I, Raitakari, Ot, Rodriguez, A, Salem, Rm, Saw, Sm, Scherag, A, Sebert, S, Siitonen, N, Simell, O, Sørensen, Ti, Sovio, U, Pourcain, B, Strachan, Dp, Sunyer, J, Taal, Hr, Teo, Yy, Thiering, E, Tiesler, C, Timpson, Nj, Uitterlinden, Ag, Valcárcel, B, Warrington, Nm, White, S, Widén, E, Willemsen, G, Wilson, Jf, Yaghootkar, H, Zeggini, E, Elks, Ce, Perry, Jr, Sulem, P, Chasman, Di, Franceschini, N, He, C, Lunetta, Kl, Visser, Ja, Byrne, Em, Gudbjartsson, Df, Esko, T, Koller, Dl, Kutalik, Z, Lin, P, Mangino, M, Marongiu, M, Mcardle, Pf, Smith, Av, Stolk, L, van Wingerden, Sh, Zhao, Jh, Albrecht, E, Corre, T, Ingelsson, E, Hayward, C, Magnusson, Pk, Smith, En, Ulivi, S, Warrington, M, Zgaga, L, Alavere, H, Amin, N, Aspelund, T, Bandinelli, S, Barroso, I, Berenson, G, Bergmann, S, Blackburn, H, Boerwinkle, E, Buring, Je, Busonero, F, Campbell, H, Chanock, Sj, Chen, W, Cornelis, Mc, Couper, D, Coviello, Ad, D'Adamo, ADAMO PIO, de Faire, U, de Geus, Ej, Deloukas, P, Döring, A, Davey Smith, G, Easton, Df, Eiriksdottir, G, Emilsson, V, Eriksson, J, Ferrucci, L, Folsom, Ar, Foroud, T, Garcia, M, Gasparini, Paolo, Gieger, C, Gudnason, V, Hall, P, Hankinson, Se, Ferreli, L, Heath, Ac, Hernandez, Dg, Hofman, A, Hu, Fb, Illig, T, Järvelin, Mr, Johnson, Ad, Karasik, D, Khaw, Kt, Kiel, Dp, Kolcic, I, Kraft, P, Launer, Lj, Laven, J, Li, S, Liu, J, Levy, D, Martin, Ng, Mcardle, Wl, Mooser, V, Murray, S, Nalls, Ma, Navarro, P, Nelis, M, Ness, Ar, Northstone, K, Oostra, Ba, Peacock, M, Palotie, A, Paré, G, Parker, An, Pedersen, Nl, Peltonen, L, Pharoah, P, Polasek, O, Plump, A, Pouta, A, Porcu, E, Rafnar, T, Rice, Jp, Ring, Sm, Rivadeneira, F, Rudan, I, Sala, C, Salomaa, V, Sanna, S, Schlessinger, D, Schork, Nj, Scuteri, A, Segrè, Av, Shuldiner, Ar, Soranzo, N, Srinivasan, Sr, Tammesoo, Ml, Tikkanen, E, Toniolo, D, Tsui, K, Tryggvadottir, L, Tyrer, J, Uda, M, van Dam, Rm, van Meurs, Jb, Vollenweider, P, Waeber, G, Wareham, Nj, Waterworth, Dm, Weedon, Mn, Wichmann, He, Wright, Af, Young, L, Zhai, G, Zhuang, Wv, Bierut, Lj, Boyd, Ha, Crisponi, L, Demerath, Ew, van Duijn, Cm, Econs, Mj, Harris, Tb, Hunter, Dj, Loos, Rj, Metspalu, A, Montgomery, Gw, Ridker, Pm, Spector, Td, Streeten, Ea, Stefansson, K, Thorsteinsdottir, U, Widen, E, Murabito, Jm, Murray, A., Hedebrand, Johannes (Beitragende*r), Hinney, Anke (Beitragende*r), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Imaging Technology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Faculteit Medische Wetenschappen/UMCG, Groningen Research Institute of Pharmacy, and Groningen Research Institute for Asthma and COPD (GRIAC)
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Male ,Netherlands Twin Register (NTR) ,Genetic Linkage ,Medizin ,Gene Expression ,Genome-wide association study ,VARIANTS ,Body Mass Index ,0302 clinical medicine ,genetic linkage ,Transforming Growth Factor beta ,Neoplasms ,molecular biology ,genetics ,Child ,Genetics (clinical) ,Adiposity ,2. Zero hunger ,0303 health sciences ,adiposity ,Mitogen-Activated Protein Kinase 3 ,Association Studies Articles ,Age Factors ,ACHONDROPLASIA ,General Medicine ,Genome-Wide Association Study ,pubertal height growth ,pubertal timing ,Phenotype ,OBESITY ,Menarche ,body height ,Female ,Signal Transduction ,medicine.medical_specialty ,age factors ,CHROMOSOME 16P11.2 ,Adolescent ,BIRTH ,Quantitative Trait Loci ,030209 endocrinology & metabolism ,Context (language use) ,Biology ,Childhood obesity ,MENARCHE ,Young Adult ,03 medical and health sciences ,AGE ,SDG 3 - Good Health and Well-being ,Prepuberty ,Internal medicine ,Genetics ,medicine ,Humans ,Molecular Biology ,030304 developmental biology ,Sign ,FACTOR RECEPTOR-3 ,MUTATIONS ,Puberty ,ta3121 ,medicine.disease ,Obesity ,Body Height ,Genetic architecture ,Endocrinology ,POPULATION COHORT ,gene expression ,Body mass index ,Follow-Up Studies - Abstract
The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P
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- 2013
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5. Rare genomic structural variants in complex disease: lessons from the replication of associations with obesity
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François Pattou, Robert Sladek, Flore Zufferey, Matthias Nauck, Kari Stefansson, Unnur Thorsteinsdottir, Robin G. Walters, Katrin Männik, Tõnu Esko, Sébastien Jacquemont, Peter Vollenweider, Jaana Laitinen, Adam J. de Smith, Claudia Schurmann, Danielle Martinet, Anna-Liisa Hartikainen, Gérard Waeber, David Meyre, Julia S. El-Sayed Moustafa, Armand Valsesia, Lachlan J. M. Coin, Philippe Froguel, Alexandra I. F. Blakemore, Henry Völzke, Marjo-Riitta Järvelin, Jacques S. Beckmann, Gudmar Thorleifsson, Aimo Ruokonen, Andres Metspalu, Paul Elliott, Beverley Balkau, and Medical Research Council (MRC)
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Male ,False discovery rate ,Heredity ,Kinesins ,lcsh:Medicine ,Genome-wide association study ,Adolescent Adult Aged Body Mass Index Child Child, Preschool *Chromosome Deletion Chromosomes, Human, Pair 16/*genetics Cohort Studies Female Forkhead Transcription Factors/genetics *Genetic Loci Genome-Wide Association Study Humans Kinesin/genetics Male Middle Aged Obesity/*genetics ,Body Mass Index ,Cohort Studies ,HIDDEN-MARKOV MODEL ,Missing heritability problem ,WIDE ASSOCIATION ,Copy-number variation ,Child ,lcsh:Science ,Genetics ,education.field_of_study ,Multidisciplinary ,Forkhead Transcription Factors ,Kinesin ,Genomics ,Middle Aged ,Child, Preschool ,Cohort ,Science & Technology - Other Topics ,Medicine ,Female ,CHILDHOOD OBESITY ,Chromosome Deletion ,Research Article ,Adult ,CHROMOSOME 16P11.2 ,Adolescent ,General Science & Technology ,Clinical Research Design ,Population ,EARLY-ONSET ,Biology ,MD Multidisciplinary ,Humans ,COHORT ,Obesity ,education ,SNP GENOTYPING DATA ,Genetic Association Studies ,COPY NUMBER VARIATION ,Aged ,Nutrition ,Science & Technology ,MULTIDISCIPLINARY SCIENCES ,Complex Traits ,lcsh:R ,Computational Biology ,Human Genetics ,Odds ratio ,BODY-MASS INDEX ,CIRCULAR BINARY SEGMENTATION ,Genetic Loci ,Case-Control Studies ,Genetics of Disease ,Multiple comparisons problem ,Structural Genomics ,lcsh:Q ,Chromosomes, Human, Pair 16 ,Genome-Wide Association Study - Abstract
The limited ability of common variants to account for the genetic contribution to complex disease has prompted searches for rare variants of large effect, to partly explain the 'missing heritability'. Analyses of genome-wide genotyping data have identified genomic structural variants (GSVs) as a source of such rare causal variants. Recent studies have reported multiple GSV loci associated with risk of obesity. We attempted to replicate these associations by similar analysis of two familial-obesity case-control cohorts and a population cohort, and detected GSVs at 11 out of 18 loci, at frequencies similar to those previously reported. Based on their reported frequencies and effect sizes (OR≥25), we had sufficient statistical power to detect the large majority (80%) of genuine associations at these loci. However, only one obesity association was replicated. Deletion of a 220 kb region on chromosome 16p11.2 has a carrier population frequency of 2×10(-4) (95% confidence interval [9.6×10(-5)-3.1×10(-4)]); accounts overall for 0.5% [0.19%-0.82%] of severe childhood obesity cases (P = 3.8×10(-10); odds ratio = 25.0 [9.9-60.6]); and results in a mean body mass index (BMI) increase of 5.8 kg.m(-2) [1.8-10.3] in adults from the general population. We also attempted replication using BMI as a quantitative trait in our population cohort; associations with BMI at or near nominal significance were detected at two further loci near KIF2B and within FOXP2, but these did not survive correction for multiple testing. These findings emphasise several issues of importance when conducting rare GSV association, including the need for careful cohort selection and replication strategy, accurate GSV identification, and appropriate correction for multiple testing and/or control of false discovery rate. Moreover, they highlight the potential difficulty in replicating rare CNV associations across different populations. Nevertheless, we show that such studies are potentially valuable for the identification of variants making an appreciable contribution to complex disease.
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- 2013
6. Extending the phenotype of recurrent rearrangements of 16p11.2: Deletions in mentally retarded patients without autism and in normal individuals
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L.A. Pérez Jurado, Ann Oostra, D. E. Fransen van de Putte, Pablo Lapunzina, Bart Loeys, B. Delle Chiaie, Marjolijn C.J. Jongmans, Johanna Lundin, K. T. Verbruggen, Rolph Pfundt, Emilia K. Bijlsma, Björn Menten, Birgit Sikkema-Raddatz, H.M. Reeser, David J. Amor, Claudia A. L. Ruivenkamp, Helene Verhelst, A. van Haeringen, Britt-Marie Anderlid, Roel Hordijk, Damien L. Bruno, Antoinet C.J. Gijsbers, Martijn H. Breuning, A. J. van Essen, Janneke H M Schuurs-Hoeijmakers, and Faculteit Medische Wetenschappen/UMCG
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Male ,MICRODUPLICATION 22Q11.2 ,Genetics and epigenetic pathways of disease [NCMLS 6] ,DNA Mutational Analysis ,Microdeletion syndrome ,Heritability of autism ,Copy-number variation ,Child ,Genetics (clinical) ,Genetics ,Comparative Genomic Hybridization ,medicine.diagnostic_test ,Learning Disabilities ,General Medicine ,Child, Preschool ,Female ,Chromosome Deletion ,Haploinsufficiency ,Adult ,Adolescent ,DISORDERS ,Chromosome 16p11.2 ,Variable phenotype ,Speech Disorders ,Genomic disorders and inherited multi-system disorders [IGMD 3] ,Young Adult ,Intellectual Disability ,medicine ,Humans ,Abnormalities, Multiple ,MICRODELETION ,Genetic Testing ,Autistic Disorder ,Genetic testing ,Family Health ,business.industry ,Infant ,medicine.disease ,POLYMORPHISM ,MICROARRAYS ,Developmental disorder ,DISCOVERY ,Autism ,business ,LEUKEMIA ,RETARDATION ,Chromosomes, Human, Pair 16 ,Comparative genomic hybridization - Abstract
Pérez-Jurado, Luis A. [et al.], Array CGH (comparative genomic hybridization) screening of large patient cohorts with mental retardation and/or multiple congenital anomalies (MR/MCA) has led to the identification of a number of new microdeletion and microduplication syndromes. Recently, a recurrent copy number variant (CNV) at chromosome 16p11.2 was reported to occur in up to 1% of autistic patients in three large autism studies. In the screening of 4284 patients with MR/MCA with various array platforms, we detected 22 individuals (14 index patients and 8 family members) with deletions in 16p11.2, which are genomically identical to those identified in the autism studies. Though some patients shared a facial resemblance and a tendency to overweight, there was no evidence for a recognizable phenotype. Autism was not the presenting feature in our series. The assembled evidence indicates that recurrent 16p11.2 deletions are associated with variable clinical outcome, most likely arising from haploinsufficiency of one or more genes. The phenotypical spectrum ranges from MR and/or MCA, autism, learning and speech problems, to a normal phenotype. © 2009 Elsevier Masson SAS. All rights reserved.
- Published
- 2009
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