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- Title
Multigene Sequencing Analysis of Children Born Small for Gestational Age With Isolated Short Stature.
- Authors
Freire, Bruna L; Homma, Thais K; Funari, Mariana F A; Lerario, Antônio M; Vasques, Gabriela A; Malaquias, Alexsandra C; Arnhold, Ivo J P; Jorge, Alexander A L
- Abstract
<bold>Context: </bold>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.<bold>Objective: </bold>To perform a genetic investigation of children with isolated short stature born SGA.<bold>Design: </bold>Screening by exome (n = 16) or targeted gene panel (n = 39) sequencing.<bold>Setting: </bold>Tertiary referral center for growth disorders.<bold>Patients and Methods: </bold>We selected 55 patients born SGA with persistent short stature without an identified cause of short stature.<bold>Main Outcome Measures: </bold>Frequency of pathogenic findings.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2019, pN.PAG
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2018-01971