Noonan syndrome patients beyond the obvious phenotype: A potential unfavorable metabolic profile
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Citações na Scopus
8
Tipo de produção
article
Data de publicação
2021
Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY
Citação
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, v.185, n.3, p.774-780, 2021
Resumo
Noonan syndrome (NS) and NS related disorders (NRD) are frequent monogenic diseases. Pathogenic variants in PTPN11 are observed in approximately 50% of these NS patients. Several pleiotropic phenotypes have previously been described in this condition. This study aimed at characterizing glucose and lipid profiles in patients with NS/NRD. We assessed fasting blood glucose, insulin, cholesterol (total and fractions), and triglyceride (TG) levels in 112 prepubertal children and 73 adults. Additionally, an oral glucose tolerance test (OGTT) was performed in 40 children and 54 adults. Data were analyzed between age groups according to the presence (+) or absence (-) of PTPN11 mutation. Prepubertal patients with NS/NRD were also compared with a control group. Despite the lean phenotype of children with NS/NRD, they presented an increased frequency of low HDL-cholesterol (63% in PTPN11+, 59% in PTPN11- and 16% in control, p < .001) and high TG levels (29% in PTPN11+, 18% in PTPN11- and 2.3% in control). PTPN11+ patients had a higher median HOMA-IR (1.0, ranged from 0.3 to 3.2) in comparison with PTPN11- (0.6; 0.2 to 4.4) and controls (0.6; 0.4 to 1.4, p = .027). Impaired glucose tolerance was observed in 19% (10:54) of lean adults with NS/NRD assessed by OGTT. Moreover, women with PTPN11 mutations had lower HDL-cholesterol levels than those without. Our results suggest that children and young adult patients with NS/NRD have an unfavorable metabolic profile characterized by low HDL, a tendency of elevated TGs, and glucose metabolism impairment despite a lean phenotype.
Palavras-chave
glucose, insulin, metabolism, Noonan syndrome, PTPN11, RASopathy
Referências
- Amer Diabet Assoc, 2013, DIABETES CARE, V36, pS67, DOI 10.2337/dc13-S067
- Binder G, 2012, J PEDIATR-US, V161, P501, DOI 10.1016/j.jpeds.2012.02.043
- da Silva FM, 2016, AM J MED GENET A, V170, P1525, DOI 10.1002/ajmg.a.37639
- da Silva RC, 2016, ARQ BRAS CARDIOL, V107, P10, DOI 10.5935/abc.20160091
- Dard L, 2018, BBA-BIOENERGETICS, V1859, P845, DOI 10.1016/j.bbabio.2018.05.003
- Elkins C, 2019, J PEDIATR HEALTH CAR, V33, P494, DOI 10.1016/j.pedhc.2019.02.009
- Faludi AA, 2017, ARQ BRAS CARDIOL, V109, P1, DOI [10.5935/abc.20170121, 10.5935/abc.20170188]
- FRIEDEWALD WT, 1972, CLIN CHEM, V18, P499
- Garcez MR, 2014, ARQ BRAS CARDIOL, V103, P476, DOI 10.5935/abc.20140156
- He Z, 2013, P NATL ACAD SCI USA, V110, pE79, DOI 10.1073/pnas.1213000110
- Hopkins PN, 2013, PHYSIOL REV, V93, P1317, DOI 10.1152/physrev.00004.2012
- Jager J, 2011, DIABETOLOGIA, V54, P180, DOI 10.1007/s00125-010-1944-0
- Jamshidi Y, 2007, ATHEROSCLEROSIS, V194, pE26, DOI 10.1016/j.atherosclerosis.2006.12.013
- Jorge AAL, 2009, HORM RES, V71, P185, DOI 10.1159/000201106
- Kuczmarski RJ, 2000, ADV DATA, V314, P1, DOI 10.1186/1475-2875-6-146
- Liu ML, 2020, CLIN NUTR, V39, P942, DOI 10.1016/j.clnu.2019.03.039
- Liu MX, 2012, BBA-MOL CELL BIOL L, V1821, P770, DOI 10.1016/j.bbalip.2011.09.020
- Lu YC, 2008, J LIPID RES, V49, P2582, DOI 10.1194/jlr.M800232-JLR200
- Malaquias AC, 2012, AM J MED GENET A, V158A, P2700, DOI 10.1002/ajmg.a.35519
- Matsuo K, 2010, J BIOL CHEM, V285, P39750, DOI 10.1074/jbc.M110.153734
- MATTHEWS DR, 1985, DIABETOLOGIA, V28, P412, DOI 10.1007/BF00280883
- NOONAN JA, 1968, AM J DIS CHILD, V116, P373, DOI 10.1001/archpedi.1968.02100020377005
- Pinto KA, 2018, PLOS ONE, V13, DOI 10.1371/journal.pone.0194190
- Tajan M, 2018, ENDOCR REV, V39, P676, DOI 10.1210/er.2017-00232
- Tajan M, 2015, EUR J MED GENET, V58, P509, DOI 10.1016/j.ejmg.2015.08.005
- Tajan M, 2014, P NATL ACAD SCI USA, V111, pE4494, DOI 10.1073/pnas.1406107111
- Tartaglia M, 2005, ANNU REV GENOM HUM G, V6, P45, DOI 10.1146/annurev.genom.6.080604.162305
- Tartaglia M, 2011, BEST PRACT RES CL EN, V25, P161, DOI 10.1016/j.beem.2010.09.002
- Tidyman William E, 2016, Curr Genet Med Rep, V4, P57
- VANDERBURGT I, 1994, AM J MED GENET, V53, P187, DOI 10.1002/ajmg.1320530213
- Wit JM, 2016, EUR J ENDOCRINOL, V174, pR145, DOI 10.1530/EJE-15-0937
- Yamamoto GL, 2015, J MED GENET, V52, P413, DOI 10.1136/jmedgenet-2015-103018
- Zhang EE, 2004, P NATL ACAD SCI USA, V101, P16064, DOI 10.1073/pnas.0405041101
- Zhang SS, 2009, P NATL ACAD SCI USA, V106, P7531, DOI 10.1073/pnas.0811715106
Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/ICr
Artigos e Materiais de Revistas Científicas - LIM/18
Artigos e Materiais de Revistas Científicas - LIM/25
Artigos e Materiais de Revistas Científicas - LIM/36
Carregar mais Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/ICr
Artigos e Materiais de Revistas Científicas - LIM/18
Artigos e Materiais de Revistas Científicas - LIM/25
Artigos e Materiais de Revistas Científicas - LIM/36