Screening for imprinting disorders in 58 patients with clinically diagnosed idiopathic short stature
-
Sayaka Kawashima
,
Masayo Kagami
and
the Japanese SHOX study group
Abstract
Objectives
Imprinted genes have important roles for normal growth and development. Imprinting disorders (IDs) such as Silver-Russell syndrome and Temple syndrome are rare diseases that typically cause short children born small for gestational age (SGA). However, some patients with short stature (SS) caused by IDs were born non-SGA. To date, the contribution of IDs to idiopathic short stature (ISS) has been poorly investigated. The aim of this study was to clarify the contribution of IDs to ISS.
Methods
We conducted methylation analysis for 10 differentially methylated regions using pyrosequencing to detect known IDs in 58 patients (31 male and 27 female children, height standard deviation score −4.2 to −2.0) carrying a clinical diagnosis of ISS.
Results
We identified no patient with IDs among these patients with ISS.
Conclusions
These results indicate that IDs are rare in patients having ISS, and that imprinted genes affect fetal growth more than postnatal growth. Because patients with IDs born non-SGA usually have clinical features characteristic of each ID, in addition to SS, the patients with ISS as a clinical diagnosis may not be associated with IDs.
It is unlikely that cases clinically diagnosed with ISS are caused by IDs leading to growth failure.
Funding source: JCR Pharmaceuticals
Funding source: National Center for Child Health and Development
Award Identifier / Grant number: 2019B-4
Funding source: Japan Agency for Medical Research and Development
Award Identifier / Grant number: 19ek0109373s0202
Funding source: Japan Society for the Promotion of Science
Award Identifier / Grant number: 18K06356
Funding source: Takeda Science Foundation
Acknowledgments
The authors are grateful to the patients and their family members for their cooperation. The authors also thank Dr. Kolba Clifford Andrew for his editorial assistance with the final draft of this paper. This work was partially supported by a research grant from JCR Pharmaceuticals. This work was supported by grants from the Japan Society for the Promotion of Science (JSPS) (18K06356), the National Center for Child Health and Development (2019B-4), the Japan Agency for Medical Research and Development (AMED) (19ek0109373s0202), and the Takeda Science Foundation.
The Japanese SHOX study group
M. Adachi (Kanagawa Children’s Medical Center), T. Tajima (Jichi Medical University), T. Tanaka (Tanaka Growth Clinic), O. Arisaka and S. Koyama (Dokkyo Medical University), T. Hamajima (Aichi Children’s Health and Medical Center), O. Nose (Nose Clinic), K. Ozono (Osaka University), N. Namba (Osaka Hospital), K. Nagasaki (Niigata University), T. Kamimaki (Shizuoka City Shimizu Hospital), S. Kanzaki (Tottori University), T. Ogata (Hamamatsu University School of Medicine), H. Tanaka (Okayama Saiseikai General Hospital), Y. Hasegawa (Tokyo Metropolitan Children’s Medical Center), K. Kobayashi (University of Yamanashi), S. Dateki (Nagasaki University), H. Mabe (Kumamoto University), I. Fujiwara (Sendai City Hospital), S. Ida (Osaka Medical Center and Research Institute for Maternal and Child Health), T. Hasegawa (Keio University), A. Uematsu (Shizuoka Children’s Hospital), K. Kashimada (Tokyo Medical and Dental University), K. Onigata (Shimane University), K. Miyako (Fukuoka Children’s Hospital), S. Yokoya (Fukushima Medical University), R. Horikawa (National Center for Child Health and Development), and M. Fukami (National Research Institute for Child Health and Development).
Research funding: MF received a research grant from JCR Pharmaceuticals. This work was also supported by grants from the Japan Society for the Promotion of Science (JSPS) (18K06356), the National Center for Child Health and Development (2019B-4), the Japan Agency for Medical Research and Development (AMED) (19ek0109373s0202), and the Takeda Science Foundation.
Author contributions: Molecular analysis was performed by SK. Detailed clinical data and materials for molecular studies were provided by HY, YH, MT, KI, SD, NN, TK, KM, and TT. The study was designed and coordinated by MK. The paper was written by SK and MK and reviewed and edited by MF.
Competing interests: The funding organization(s) played no role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, nor in the decision to submit the report for publication.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: This study has complied with all the relevant national regulations, institutional policies, and was in accordance with the tenets of the Helsinki Declaration. It has been approved by the Institutional Review Board of the National Center for Child Health and Development, Tokyo, Japan, and was performed after obtaining written informed consent forms from all the participants or legal guardians.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2020-0198).
© 2020 Walter de Gruyter GmbH, Berlin/Boston
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- Frontmatter
- Research Articles
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- Cascade screening and treatment of children with familial hypercholesterolemia in Turkey
- Risk of adrenal insufficiency following intra-articular or periarticular corticosteroid injections among children with chronic arthritis
- Vitamin D status is related to severity at onset of diabetes and worse glycemic control
- Reassessing vitamin D supplementation in preterm infants: a prospective study and review of the literature
- Mutations in PMM2 gene in four unrelated Spanish families with polycystic kidney disease and hyperinsulinemic hypoglycemia
- Liraglutide pharmacokinetics and exposure-response in pediatric patients with type 2 diabetes
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- Prevalence of autoantibodies in type 1 diabetes mellitus pediatrics in Mazandaran, North of Iran
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- Ambulatory blood pressure profile in office normotensive obese children: prevalence of masked hypertension and impact of parental hypertension
- Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review
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- Case Reports
- ROHHAD syndrome – A still unrecognized cause of childhood obesity: report of three cases
- Carbonic anhydrase VA deficiency: a very rare case of hyperammonemic encephalopathy
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