Targeted NGS achieves 28% diagnostic yield in pediatric short stature
The study reports a retrospective analysis of targeted next-generation sequencing using an 185-gene panel in 64 children with short stature. Investigators found a 28.1% diagnostic yield for pathogenic or likely pathogenic variants, distributed across 25 genes with FLNB and OBSL1 being the most frequent. Patients carrying these variants showed significantly lower birth weight, higher rates of parental consanguinity, and a reduced gap between bone and chronological age. These findings indicate that targeted NGS can clarify etiology in a substantial subset of cases and suggest that specific clinical features may help laboratories and clinicians prioritize genetic testing.
The original study
Genotype-phenotype correlations in children with short stature: results of targeted next-generation sequencing.
- Authors
- Meral R, Er E, Filibeli BE, Kırbıyık Ö, Güvenç MS, Dündar BN
- Journal
- Journal of pediatric endocrinology & metabolism : JPEM
- Type
- Journal Article
- PMID
- 42446396
Original abstract
OBJECTIVES: Short stature is a frequent reason for referral to pediatric endocrinology clinics, and its underlying cause often remains unclear. This study aimed to determine the diagnostic yield of targeted next-generation sequencing (NGS) and to evaluate genotype-phenotype correlations in children with short stature. METHODS: This retrospective observational study included 64 children (37 males, 27 females) with short stature (height < -2 SDS) who underwent targeted NGS using a 185-gene panel. Patients were divided into two groups: those with pathogenic or likely pathogenic variants and all remaining patients. Clinical and anthropometric characteristics were compared between groups. RESULTS: Genetic variants were identified in 31 patients (48.4 %), and pathogenic or likely pathogenic variants in 18, corresponding to a diagnostic yield of 28.1 %. Variants were distributed across 25 genes, most frequently FLNB (n=3) and OBSL1 (n=2). Compared with others, patients with pathogenic or likely pathogenic variants had lower birth weight SDS (-1.69 ± 1.73 vs. -0.56 ± 1.08, p=0.046), higher consanguinity (50 % vs. 13 %, p=0.007), and a smaller difference between bone age and chronological age (p=0.031). No differences were found in height SDS, parental height, or target height. CONCLUSIONS: Targeted NGS provides a substantial diagnostic yield in children with short stature and reveals marked genetic heterogeneity. Clinical features such as consanguinity and lower birth weight may help identify patients with a higher likelihood of a genetic etiology. These findings support the integration of genetic testing into the diagnostic evaluation of selected patients with short stature.