Lukas Plachy 1 , Petra Dusatkova 1 , Klara Maratova 1 , Lenka Petruzelkova 1 , Dana Zemkova 1 , Lenka Elblova 1 , Petra Kucerova 1 , Ledjona Toni 1 , Stanislava Kolouskova 1 , Marta Snajderova 1 , Zdenek Sumnik 1 , Jan Lebl 1 , Stepanka Pruhova 1 Show Affiliations »
Abstract
CONTEXT: The C-type natriuretic peptide receptor encoded by the NPR2 gene is a paracrine regulator of the growth plate; heterozygous NPR2 variants cause short stature with possible presence of different signs of bone dysplasia. To date, the effect of growth hormone (GH) treatment has been described in a few individuals with NPR2 gene variants with inconsistent results. OBJECTIVES: To identify NPR2 gene variants among children with familial short stature (FSS) and to describe their phenotype, including GH treatment response. DESIGN, SETTINGS AND PATIENTS: Out of 747 patients with short stature treated with GH in a single center, 87 with FSS met the inclusion criteria (pretreatment height ≤ -2 standard deviation in both the patient and the shorter parent, unknown genetic etiology). Next-generation sequencing methods were performed to search for NPR2 gene variants. The results were evaluated using the American College of Medical Genetics and Genomics guidelines. The GH treatment response (growth velocity improvement and height standard deviation score development over the first 5 years of treatment) was evaluated. RESULTS: In 5/87 children (5.7%), a (likely) pathogenic variant in the NPR2 gene was identified (p.Ile558Thr [in 2], p.Arg205*, p.Arg557His, p.Ser603Thr). Two children had disproportionate short-limbed short stature, 1 a dysplastic 5th finger phalanx. The growth velocity in the first year of GH treatment accelerated by 3.6 to 4.2 cm/year; the height improved by 1.2 to 1.8 SD over 5 years of treatment. CONCLUSIONS: NPR2 gene variants cause FSS in a significant proportion of children. Their GH treatment response is promising. Studies including final height data are necessary to assess the long-term efficacy of this therapy. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
CONTEXT: The C-type natriuretic peptide receptor encoded by the NPR2 gene is a paracrine regulator of the growth plate; heterozygous NPR2 variants cause short stature with possible presence of different signs of bone dysplasia . To date, the effect of growth hormone (GH ) treatment has been described in a few individuals with NPR2 gene variants with inconsistent results. OBJECTIVES: To identify NPR2 gene variants among children with familial short stature (FSS ) and to describe their phenotype, including GH treatment response. DESIGN, SETTINGS AND PATIENTS : Out of 747 patients with short stature treated with GH in a single center, 87 with FSS met the inclusion criteria (pretreatment height ≤ -2 standard deviation in both the patient and the shorter parent, unknown genetic etiology). Next-generation sequencing methods were performed to search for NPR2 gene variants. The results were evaluated using the American College of Medical Genetics and Genomics guidelines. The GH treatment response (growth velocity improvement and height standard deviation score development over the first 5 years of treatment) was evaluated. RESULTS: In 5/87 children (5.7%), a (likely) pathogenic variant in the NPR2 gene was identified (p.Ile558Thr [in 2], p.Arg205* , p.Arg557His , p.Ser603Thr ). Two children had disproportionate short-limbed short stature, 1 a dysplastic 5th finger phalanx. The growth velocity in the first year of GH treatment accelerated by 3.6 to 4.2 cm/year; the height improved by 1.2 to 1.8 SD over 5 years of treatment. CONCLUSIONS: NPR2 gene variants cause FSS in a significant proportion of children . Their GH treatment response is promising. Studies including final height data are necessary to assess the long-term efficacy of this therapy. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Entities: Chemical
Disease
Gene
Mutation
Species
Keywords:
NPR2; familial short stature; growth hormone treatment; growth plate disorders; next-generation sequencing
Year: 2020
PMID： 31990356 DOI： 10.1210/clinem/dgaa037
Source DB: PubMed Journal: J Clin Endocrinol Metab ISSN： 0021-972X Impact factor: 5.958