Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844-848

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art_KOCZKOWSKA_GenotypePhenotype_Correlation_in_NF1_Evidence_for_a_More_2018.PDF (764.92 KB)
Citações na Scopus
140
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
CELL PRESS
Autores
KOCZKOWSKA, Magdalena
CHEN, Yunjia
CALLENS, Tom
GOMES, Alicia
SHARP, Angela
JOHNSON, Sherrell
HSIAO, Meng-Chang
CHEN, Zhenbin
BALASUBRAMANIAN, Meena
BARNETT, Christopher P.
Citação
AMERICAN JOURNAL OF HUMAN GENETICS, v.102, n.1, p.69-87, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1: 2,000-3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p. Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons-Leu844, Cys845, Ala846, Leu847, and Gly848-located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect similar to 0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844-848 exists and will be valuable in the management and genetic counseling of a significant number of individuals.
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URI
https://observatorio.fm.usp.br/handle/OPI/24955
Referências
  1. BALLESTER R, 1990, CELL, V63, P851, DOI 10.1016/0092-8674(90)90151-4
  2. Bertola DR, 2005, AM J MED GENET A, V136A, P242, DOI 10.1002/ajmg.a.30813
  3. Blanchard G, 2016, EUR J PAEDIATR NEURO, V20, P275, DOI 10.1016/j.ejpn.2015.12.002
  4. Blazo MA, 2004, AM J MED GENET A, V127A, P224, DOI 10.1002/ajmg.a.20650
  5. Brems H, 2007, NAT GENET, V39, P1120, DOI 10.1038/ng2113
  6. Brems H, 2009, LANCET ONCOL, V10, P508, DOI 10.1016/S1470-2045(09)70033-6
  7. Chang T, 2012, NEUROFIBROMATOSIS TY, V1, P469
  8. Cnossen MH, 1998, ARCH DIS CHILD, V78, P408, DOI 10.1136/adc.78.5.408
  9. Crucis A, 2015, PEDIATR BLOOD CANCER, V62, P1733, DOI 10.1002/pbc.25556
  10. Cunha KS, 2016, GENES-BASEL, V7, DOI 10.3390/genes7120133
  11. DeBella K, 2000, PEDIATRICS, V105, P608, DOI 10.1542/peds.105.3.608
  12. DECLUE JE, 1991, P NATL ACAD SCI USA, V88, P9914, DOI 10.1073/pnas.88.22.9914
  13. EASTON DF, 1993, AM J HUM GENET, V53, P305
  14. Ekvall S, 2014, AM J MED GENET A, V164, P579, DOI 10.1002/ajmg.a.36313
  15. Evans DG, 2010, AM J MED GENET A, V152A, P327, DOI 10.1002/ajmg.a.33139
  16. Evans DGR, 2002, J MED GENET, V39, P311, DOI 10.1136/jmg.39.5.311
  17. Fahsold R, 2000, AM J HUM GENET, V66, P790, DOI 10.1086/302809
  18. Ferner RE, 2007, J MED GENET, V44, P81, DOI 10.1136/jmg.2006.045906
  19. Friedman JM, 1997, AM J MED GENET, V70, P138, DOI 10.1002/(SICI)1096-8628(19970516)70:2<138::AID-AJMG7>3.0.CO;2-U
  20. HUSON SM, 1989, J MED GENET, V26, P704, DOI 10.1136/jmg.26.11.704
  21. HUSON SM, 1988, BRAIN, V111, P1355, DOI 10.1093/brain/111.6.1355
  22. HUSON SM, 1989, J MED GENET, V26, P712, DOI 10.1136/jmg.26.11.712
  23. Jahraus CD, 2006, PEDIATR BLOOD CANCER, V46, P586, DOI 10.1002/pbc.20655
  24. Kamat MA, 2016, HUM MUTAT, V37, P65, DOI 10.1002/humu.22917
  25. Kehrer-Sawatzki H, 2017, HUM GENET, V136, P349, DOI 10.1007/s00439-017-1766-y
  26. Khosrotehrani K, 2005, AM J MED GENET A, V132A, P49, DOI 10.1002/ajmg.a.30394
  27. Kluwe L, 2003, J MED GENET, V40, P368, DOI 10.1136/jmg.40.5.368
  28. Korf BR, 1999, AM J MED GENET, V89, P31, DOI 10.1002/(SICI)1096-8628(19990326)89:1<31::AID-AJMG7>3.0.CO;2-W
  29. Krab LC, 2008, JAMA-J AM MED ASSOC, V300, P287, DOI 10.1001/jama.300.3.287
  30. Lammert M, 2005, ARCH DERMATOL, V141, P71, DOI 10.1001/archderm.141.1.71
  31. Li KR, 2016, DIS MODEL MECH, V9, P759, DOI 10.1242/dmm.025783
  32. Lin AE, 2000, AM J MED GENET, V95, P108, DOI 10.1002/1096-8628(20001113)95:2<108::AID-AJMG4>3.0.CO;2-0
  33. LISTERNICK R, 1994, J PEDIATR-US, V125, P63, DOI 10.1016/S0022-3476(94)70122-9
  34. Listernick R, 2007, ANN NEUROL, V61, P189, DOI 10.1002/ana.21107
  35. Mangoura D, 2006, ONCOGENE, V25, P735, DOI 10.1038/sj.onc.1209113
  36. Mautner VF, 2010, J MED GENET, V47, P623, DOI 10.1136/jmg.2009.075937
  37. McCoughan A, 2007, J MED GENET, V44, P463, DOI 10.1136/jmg.2006.048140
  38. McGaughran JM, 1999, J MED GENET, V36, P197
  39. McPherson JR, 2015, CANCER MED-US, V4, P1871, DOI 10.1002/cam4.551
  40. Messiaen L, 2003, J MED GENET, V40, P122, DOI 10.1136/jmg.40.2.122
  41. Messiaen L. M., 2012, ADV NEUROFIBROMATOSI, P89
  42. Xie J., 2012, NEUROFIBROMATOSIS TY, P151
  43. Messiaen LM, 2000, HUM MUTAT, V15, P541, DOI 10.1002/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N
  44. MESSIAEN LM, 2008, NEUROFIBROMATOSES, V16, P63
  45. Messiaen L, 2009, JAMA-J AM MED ASSOC, V302, P2111, DOI 10.1001/jama.2009.1663
  46. [Anonymous], 1988, ARCH NEUROL-CHICAGO, V45, P575, DOI 10.1097/00005537-199606000-00007
  47. NELLHAUS G, 1968, PEDIATRICS, V41, P106
  48. Ng PC, 2001, GENOME RES, V11, P863, DOI 10.1101/gr.176601
  49. Nicolin G, 2009, PEDIATR BLOOD CANCER, V53, P1231, DOI 10.1002/pbc.22198
  50. Nystrom AM, 2009, ACTA PAEDIATR, V98, P693, DOI 10.1111/j.1651-2227.2008.01170.x
  51. Pascual-Castroviejo I, 2007, NEUROPEDIATRICS, V38, P105, DOI 10.1055/s-2007-985136
  52. Pasmant E., 2012, NEUROFIBROMATOSIS TY, P269
  53. Pasmant E, 2011, FASEB J, V25, P444, DOI 10.1096/fj.10-172452
  54. Patil S, 2012, ONCOLOGIST, V17, P101, DOI 10.1634/theoncologist.2010-0181
  55. Poyhonen M., 2012, NEUROFIBROMATOSIS TY, P17
  56. Pemov A, 2014, PLOS GENET, V10, DOI 10.1371/journal.pgen.1004575
  57. Pinna V, 2015, EUR J HUM GENET, V23, P1068, DOI 10.1038/ejhg.2014.243
  58. Plotkin SR, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0035711
  59. Prada CE, 2012, J PEDIATR-US, V160, P461, DOI 10.1016/j.jpeds.2011.08.051
  60. PULST SM, 1991, NEUROLOGY, V41, P1923, DOI 10.1212/WNL.41.12.1923
  61. Rasmussen SA, 2000, AM J EPIDEMIOL, V151, P33
  62. Richards S, 2015, GENET MED, V17, P405, DOI 10.1038/gim.2015.30
  63. Rojnueangnit K, 2015, HUM MUTAT, V36, P1052, DOI 10.1002/humu.22832
  64. Rost B, 2004, NUCLEIC ACIDS RES, V32, pW321, DOI 10.1093/nar/gkh377
  65. Ruggieri M, 2015, CLIN GENET, V87, P401, DOI 10.1111/cge.12498
  66. Sabbagh A, 2013, HUM MUTAT, V34, P1510, DOI 10.1002/humu.22392
  67. Sabbagh A, 2009, HUM MOL GENET, V18, P2768, DOI 10.1093/hmg/ddp212
  68. Santoro C, 2015, EUR J HUM GENET, V23, P1460, DOI 10.1038/ejhg.2015.93
  69. Seminog OO, 2013, BRIT J CANCER, V108, P193, DOI 10.1038/bjc.2012.535
  70. Stevenson DA, 2011, AM J MED GENET C, V157C, P90, DOI 10.1002/ajmg.c.30296
  71. Sung L, 2004, J PEDIATR-US, V144, P666, DOI 10.1016/j.jpeds.2004.02.026
  72. Szudek J, 2002, GENET EPIDEMIOL, V23, P150, DOI 10.1002/gepi.01129
  73. Terry AR, 2013, AM J OBSTET GYNECOL, V209, DOI 10.1016/j.ajog.2013.03.029
  74. Thakker SD, 1999, NEURORADIOLOGY, V41, P625, DOI 10.1007/s002340050814
  75. Tonsgard JH, 1998, NEUROLOGY, V50, P1755, DOI 10.1212/WNL.50.6.1755
  76. Toonen JA, 2016, HUM MOL GENET, V25, P1703, DOI 10.1093/hmg/ddw039
  77. Duong TA, 2011, ORPHANET J RARE DIS, V6, DOI 10.1186/1750-1172-6-18
  78. Tucker T, 2005, NEUROLOGY, V65, P205, DOI 10.1212/01.wnl.0000168830.79997.13
  79. Upadhyaya M, 2007, AM J HUM GENET, V80, P140, DOI 10.1086/510781
  80. Upadhyaya M, 2009, NEUROGENETICS, V10, P251, DOI 10.1007/s10048-009-0178-0
  81. Uusitalo E, 2016, J CLIN ONCOL, V34, P1978, DOI 10.1200/JCO.2015.65.3576
  82. Uusitalo E, 2015, J INVEST DERMATOL, V135, P904, DOI 10.1038/jid.2014.465
  83. van Minkelen R, 2014, CLIN GENET, V85, P318, DOI 10.1111/cge.12187
  84. VanEs S, 1996, PEDIATR RADIOL, V26, P478, DOI 10.1007/BF01377205
  85. Vargiami E, 2004, J PEDIATR-US, V145, P859, DOI 10.1016/j.jpeds.2004.06.013
  86. Waggoner DJ, 2000, AM J MED GENET, V92, P132, DOI 10.1002/(SICI)1096-8628(20000515)92:2<132::AID-AJMG10>3.0.CO;2-6
  87. Williams VC, 2009, PEDIATRICS, V123, P124, DOI 10.1542/peds.2007-3204
  88. Wright EMMB, 2013, J MED GENET, V50, P606, DOI 10.1136/jmedgenet-2013-101648
  89. Zhou X, 2016, NAT GENET, V48, P4, DOI 10.1038/ng.3466

Coleções
Artigos e Materiais de Revistas Científicas - HC/ICr
Artigos e Materiais de Revistas Científicas - LIM/36