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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 8
[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
Total Affiliations: 4
Document type: Journal article
Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 104, n. 6, p. 2023-2030, JUN 2019.
Web of Science Citations: 2

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)

FAPESP's process: 13/03236-5 - New approaches and methodologies in molecular-genetic studies of growth and pubertal development disorders
Grantee:Alexander Augusto de Lima Jorge
Support type: Research Projects - Thematic Grants
FAPESP's process: 15/26980-7 - Genetic causes of prenatal onset growth disorder
Grantee:Thais Kataoka Homma
Support type: Scholarships in Brazil - Doctorate