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de Albuquerque Albuquerque, Edoarda Vasco ^[1] ; de Assis Funari, Mariana Ferreira ^[2] ; de Souza Quedas, Elisangela Pereira ^[1] ; Honjo Kawahira, Rachel Sayuri ^[3] ; Jallad, Raquel Soares ^[4] ; Homma, Thais Kataoka ^[1] ; Martin, Regina Matsunaga ^{[2, 5]} ; Brito, Vinicius Nahime ^[2] ; Malaquias, Alexsandra Christianne ^{[1, 6]} ; Lerario, Antonio Marcondes ^{[7, 1]} ; Rosenberg, Carla ^[8] ; Victorino Krepischi, Ana Cristina ^[8] ; Kim, Chong Ae ^[3] ; Prado Arnhold, Ivo Jorge ^[2] ; de Lima Jorge, Alexander Augusto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Hosp Clin Fac Med, Unidade Endocrinol Genet LIM25, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Hosp Clin Fac Med, Unidade Endocrinol Desenvolvimento, Lab Hormonios & Genet Mol LIM42, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Hosp Clin Fac Med, Unidade Genet Inst Crianca, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Unidade Neuroendocrinol, Hosp Clin Fac Med, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Unidade Doencas Osteometab, Hosp Clin Fac Med, Sao Paulo, SP - Brazil

^[6] Irmandade Santa Casa Misericordia Sao Paulo, Dept Pediat, Unidade Endocrinol Pediat, Sao Paulo, SP - Brazil

^[7] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 - USA

^[8] Univ Sao Paulo, IB, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 182, n. 2, p. 139-147, FEB 2020.
• Citações Web of Science: 0

Resumo

Context: Patients with tall stature often remain undiagnosed after clinical investigation and few studies have genetically assessed this group, most of them without a systematic approach. Objective: To assess prospectively a group of individuals with tall stature, with and without syndromic features, and to establish a molecular diagnosis for their growth disorder. Design: Screening by karyotype (n = 42), chromosome microarray analyses (CMA) (n = 16), MS-MLPA (n = 2) targeted panel (n = 12) and whole-exome sequencing (n = 31). Patients and methods: We selected 42 patients with tall stature after exclusion of pathologies in GH/IGF1 axis and divided them into syndromic (n = 30) and non-syndromic (n = 12) subgroups. Main outcome measures: Frequencies of pathogenic findings. Results: We identified two patients with chromosomal abnormalities including SHOX trisomy by karyotype, one 9q22.3 microdeletion syndrome by CMA, two cases of Beckwith-Wiedemann syndrome by targeted MS-MLPA analysis and nine cases with heterozygous pathogenic or likely pathogenic genetic variants by multigene analysis techniques (FBN1 = 3, NSD1 = 2, NFIX = 1, SUZ12 = 1, CHD8 = 1, MC4R = 1). Three of 20 patients analyzed by WES had their diagnosis established. Only one non-syndromic patient had a definitive diagnosis. The sequential genetic assessment diagnosed 14 out of 42 (33.3%) tall patients. Conclusion: A systematic molecular approach of patients with tall stature was able to identify the etiology in 13 out of 30 (43.3%) syndromic and 1 out of 12 (8.3%) non-syndromic patients, contributing to the genetic counseling and avoiding unfavorable outcomes in the syndromic subgroup. (AU)

• Processo FAPESP: 14/50137-5 - Caracterização molecular de doenças monogênicas do desenvolvimento por sequenciamento em larga escala
• Beneficiário: Berenice Bilharinho de Mendonça
• Modalidade de apoio: 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
• Modalidade de apoio: Auxílio à Pesquisa - Temático