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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Freire, Bruna L. [1, 2] ; Homma, Thais K. [1, 2] ; Funari, Mariana F. A. [2] ; Lerario, Antonio M. [3] ; Vasques, Gabriela A. [1, 2] ; Malaquias, Alexsandra C. [1, 4] ; Arnhold, Ivo J. P. [2] ; Jorge, Alexander A. L. [1, 2]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Med, Lab Endocrinol Celular & Mol LIM25, Disciplina Endocrinol, Unidade Endocrinol Genet, Ave Dr Arnaldo, 455 5 Andar Sala 5340, BR-01246903 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Lab Hormonios & Genet Mol LIM42, Unidade Endocrinol Desenvolvimento, Hosp Clin, BR-01246903 Sao Paulo - Brazil
[3] Univ Michigan, Div Metab Endocrinol & Diabet, Dept Internal Med, Ann Arbor, MI 48109 - USA
[4] Fac Ciencias Med Santa Casa Sao Paulo, Irmandade Santa Casa Misericordia Sao Paulo, Dept Pediat, Unidade Endocrinol Pediat, BR-01221020 Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 104, n. 6, p. 2023-2030, JUN 2019.
Citações Web of Science: 2
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. (AU)

Processo FAPESP: 14/50137-5 - Caracterização molecular de doenças monogênicas do desenvolvimento por sequenciamento em larga escala
Beneficiário:Berenice Bilharinho de Mendonça
Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
Processo FAPESP: 13/03236-5 - Novas abordagens e metodologias na investigação genético-molecular dos distúrbios de crescimento e desenvolvimento puberal
Beneficiário:Alexander Augusto de Lima Jorge
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 15/26980-7 - Causas genéticas de distúrbio de crescimento de início pré-natal
Beneficiário:Thais Kataoka Homma
Linha de fomento: Bolsas no Brasil - Doutorado