Abstract
NPR2 variants are associated with various short stature and bone dysplasia, such as acromesomelic dysplasia Maroteaux tyoe, individuals with a phenotype similar to Léri-Weill syndrome (LWD), and idiopathic short stature (ISS). However, few studies have reported on the relationship between familial short stature (FSS) and NPR2 variants. This study aimed to explore the relationship between FSS and NPR2 variants through the detection and identification of NPR2 variants in children with FSS, phenotypic description, clear treatment plan, and follow-up of treatment effect. Children who met the FSS diagnostic criteria and had informed consent were included in the study. The trio whole-exome sequencing method (trio-WES) was used to detect and evaluate the NPR2 variants. A total of 16 children with short stature were included in this study (pretreatment height≤-2 standard deviation (SD) in both the patient and the shorter parent, unknown genetic etiology). NPR2 variants were identified in 12.5%(2/16) of the participants. Patient A was a 6-year-old male and 103.7cm tall (-3.11SD), while Patient B was a 9-year-old female and 123.2cm tall (-1.88SD). However, their heights increased after recombinant human growth hormone (rhGH) treatment. The height of patient A increased by 0.36SD six months after treatment while that of patient B increased by 1.22SD after one and a half years of treatment. NPR2 variant causes FSS. The growth rate of children significantly improved after rhGH treatment. However, further follow-up study is needed to determine the final height after long-term treatment.
Highlights
Short stature is described as having less than two standard deviations (SD) of the average height of the same race, age, and gender [1]
Analysis was conducted on 16 familial short stature (FSS) (10 males, average height of −2.42 ± 0.52SD and six females, the average height of −2.55 ± 0.63SD, the average age was 6.32 ± 2.28 years), and two NPR2 variant cases, accounting for 12.5% of FSS children
Human height mainly depends on the growth of long bones via endochondral osteogenesis
Summary
Short stature is described as having less than two standard deviations (SD) of the average height of the same race, age, and gender [1]. While Idiopathic short stature (ISS) accounts for between 60 and 80% of short stature, its specific etiology is unknown [2]. ISS can be divided into familial short stature (FSS) or nonfamilial idiopathic short stature based on the international classification of pediatric endocrine diagnosis [3]. Growth hormone (GH) – insulin-like growth factor (IGF)-I axis is essential for regulating bone formation during growth. The abnormal gene at each level of the axis affects the axis, causing short stature [5, 6]. The GH-IGF-1 axis was considered as the nuclear type axis regulating the growth of children. With the rapid development of science and technology, some recent studies have shown that several factors affect growth and development. The genome-wide association studies (GWS) have shown the presence of about 180 genetic loci with several variations associated with human
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