Multigene Sequencing Analysis of Children Born Small for Gestational Age With Isolated Short Stature

Imagem de Miniatura
Arquivos
art_FREIRE_Multigene_Sequencing_Analysis_of_Children_Born_Small_for_2019.PDF (665.7 KB)
Citações na Scopus
53
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ENDOCRINE SOC
Autores
LERARIO, Antonio M.
Citação
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v.104, n.6, p.2023-2030, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Context: Patients born small for gestational age (SGA) who present with persistent short stature could have an underlying genetic etiology that will account for prenatal and postnatal growth impairment. We applied a unique massive parallel sequencing approach in cohort of patients with exclusively nonsyndromic SGA to simultaneously interrogate for clinically substantial genetic variants. Objective: To perform a genetic investigation of children with isolated short stature born SGA. Design: Screening by exome (n = 16) or targeted gene panel (n = 39) sequencing. Setting: Tertiary referral center for growth disorders. Patients and Methods: We selected 55 patients born SGA with persistent short stature without an identified cause of short stature. Main Outcome Measures: Frequency of pathogenic findings. Results: We identified heterozygous pathogenic or likely pathogenic genetic variants in 8 of 55 patients, all in genes already associated with growth disorders. Four of the genes are associated with growth plate development, IHH (n = 2), NPR2 (n = 2), SHOX (n = 1), and ACAN (n = 1), and two are involved in the RAS/MAPK pathway, PTPN11 (n = 1) and NF1 (n = 1). None of these patients had clinical findings that allowed for a clinical diagnosis. Seven patients were SGA only for length and one was SGA for both length and weight. Conclusion: These genomic approaches identified pathogenic or likely pathogenic genetic variants in 8 of 55 patients (15%). Six of the eight patients carried variants in genes associated with growth plate development, indicating that mild forms of skeletal dysplasia could be a cause of growth disorders in this group of patients.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/32996
Referências
  1. Alam K, 2018, EUR J HUM GENET, V26, P1241, DOI 10.1038/s41431-018-0175-6
  2. Blum WF, 2013, J CLIN ENDOCR METAB, V98, pE1383, DOI 10.1210/jc.2013-1222
  3. Boguszewski MCS, 2011, BMC PEDIATR, V11, DOI 10.1186/1471-2431-11-66
  4. Caliebe J, 2012, HORM RES PAEDIAT, V77, P250, DOI 10.1159/000338341
  5. Canton APM, 2014, EUR J ENDOCRINOL, V171, P253, DOI 10.1530/EJE-14-0232
  6. de Bruin C, 2016, HORM RES PAEDIAT, V86, P342, DOI 10.1159/000446476
  7. de Graaff LCG, 2013, HORM RES PAEDIAT, V80, P466, DOI 10.1159/000355409
  8. Dillon OJ, 2018, EUR J HUM GENET, V26, P644, DOI 10.1038/s41431-018-0099-1
  9. Ester WA, 2009, J CLIN ENDOCR METAB, V94, P4717, DOI 10.1210/jc.2008-1502
  10. Fenton TR, 2013, BMC PEDIATR, V13, DOI 10.1186/1471-2431-13-59
  11. Finken MJJ, 2018, ENDOCR REV, V39, P851, DOI 10.1210/er.2018-00083
  12. Fredriks AM, 2005, ARCH DIS CHILD, V90, P807, DOI 10.1136/adc.2004.050799
  13. Freire BL, 2018, RES GATE, DOI [10.13140/RG.2.2.19924.65929/1, DOI 10.13140/RG.2.2.19924.65929/1]
  14. Freire BL, 2018, RES GATE, DOI [10.13140/RG.2.2.24760.39681, DOI 10.13140/RG.2.2.24760.39681]
  15. Friedman J, 1993, GENEREVIEWS R
  16. Fujimoto M, 2015, CLIN ENDOCRINOL, V83, P834, DOI 10.1111/cen.12791
  17. Gkourogianni A, 2017, J CLIN ENDOCR METAB, V102, P460, DOI 10.1210/jc.2016-3313
  18. Gravholt CH, 2017, EUR J ENDOCRINOL, V177, pG1, DOI 10.1530/EJE-17-0430
  19. Greulich WW, 1959, RADIOGRAPHIC ATLAS S
  20. Guo MH, 2014, HORM RES PAEDIAT, V82, P44, DOI 10.1159/000360857
  21. Hattori A, 2017, ENDOCR J, V64, P947, DOI 10.1507/endocrj.EJ17-0150
  22. Hauer NN, 2018, GENET MED, V20, P630, DOI 10.1038/gim.2017.159
  23. Hauer NN, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-12465-6
  24. HOYME HE, 1987, AM J DIS CHILD, V141, P947, DOI 10.1001/archpedi.1987.04460090024014
  25. Huang Z, 2018, CELL PHYSIOL BIOCHEM, V49, P295, DOI 10.1159/000492879
  26. Kim YM, 2017, CLIN GENET, V92, P594, DOI 10.1111/cge.13038
  27. Kuczmarski R J, 2000, Adv Data, P1
  28. Lee PA, 2003, PEDIATRICS, V111, P1253, DOI 10.1542/peds.111.6.1253
  29. Malaquias AC, 2013, HORM RES PAEDIAT, V80, P449, DOI 10.1159/000355411
  30. Marchini A, 2016, ENDOCR REV, V37, P417, DOI 10.1210/er.2016-1036
  31. Marouli E, 2017, NATURE, V542, P186, DOI 10.1038/nature21039
  32. Ocaranza P, 2017, HORM RES PAEDIAT, V87, P412, DOI 10.1159/000464143
  33. Pannone L, 2017, HUM MUTAT, V38, P451, DOI 10.1002/humu.23175
  34. Renes JS, 2013, J CLIN ENDOCR METAB, V98, P3932, DOI 10.1210/jc.2013-2491
  35. Richards S, 2015, GENET MED, V17, P405, DOI 10.1038/gim.2015.30
  36. Roberts AE, 2013, LANCET, V381, P333, DOI 10.1016/S0140-6736(12)61023-X
  37. Seaver LF, 2009, GENET MED, V11, P765
  38. Soellner L, 2013, J PEDIATR GENET, V2, P113, DOI 10.3233/PGE-13059
  39. Stark Z, 2017, GENET MED, V19, P867, DOI 10.1038/gim.2016.221
  40. Tatsi C, 2017, J ENDOCR SOC, V1, P1006, DOI 10.1210/js.2017-00229
  41. van der Steen M, 2017, J CLIN ENDOCR METAB, V102, P1458, DOI 10.1210/jc.2016-2941
  42. Vasques GA, 2018, J CLIN ENDOCR METAB, V103, P604, DOI 10.1210/jc.2017-02026
  43. Vasques GA, 2014, HORM RES PAEDIAT, V82, P222, DOI 10.1159/000365049
  44. Vasques GA, 2013, J CLIN ENDOCR METAB, V98, pE1636, DOI 10.1210/jc.2013-2142
  45. Wang SR, 2015, HUM MUTAT, V36, P474, DOI 10.1002/humu.22773
  46. Wang SR, 2013, J CLIN ENDOCR METAB, V98, pE1428, DOI 10.1210/jc.2013-1534
  47. Wit JM, 2016, EUR J ENDOCRINOL, V174, pR145, DOI 10.1530/EJE-15-0937

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/25
Artigos e Materiais de Revistas Científicas - LIM/42