Multigene Sequencing Analysis of Children Born Small for Gestational Age With Isolated Short Stature.
J Clin Endocrinol Metab
; 104(6): 2023-2030, 2019 06 01.
Article
en En
| MEDLINE
| ID: mdl-30602027
ABSTRACT
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 ANDMETHODS:
We selected 55 patients born SGA with persistent short stature without an identified cause of short stature. MAIN OUTCOMEMEASURES:
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Estatura
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Recién Nacido Pequeño para la Edad Gestacional
/
Secuenciación de Nucleótidos de Alto Rendimiento
/
Trastornos del Crecimiento
Tipo de estudio:
Evaluation_studies
/
Prognostic_studies
Límite:
Child
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Child, preschool
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Female
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Humans
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Male
/
Newborn
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2019
Tipo del documento:
Article
País de afiliación:
Brasil