Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Mar 6, 2021; 9(7): 1600-1609
Published online Mar 6, 2021. doi: 10.12998/wjcc.v9.i7.1600
Study on pathogenic genes of dwarfism disease by next-generation sequencing
Lv-Lv Yang, Shi-Shan Liang
Lv-Lv Yang, Shi-Shan Liang, Department of Pediatrics, Quanzhou First Hospital, Quanzhou 362000, Fujian Province, China
Author contributions: Yang LL designed the study and performed the research; Liang SS analyzed the data; Yang LL wrote the paper and revised the manuscript for final submission.
Supported by Quanzhou Science and Technology Bureau, No. 2018Z072
Institutional review board statement: The study was reviewed and approved by the Quanzhou First Hospital Review Board.
Informed consent statement: All study participants or their legal guardian provided written informed consent prior to study enrollment.
Conflict-of-interest statement: We declare that we have no financial or personal relationships with other individuals or organizations that can inappropriately influence our work and that there is no professional or other personal interest of any nature in any product, service and/or company that could be construed as influencing the position presented in or the review of the manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Lv-Lv Yang, MD, Doctor, Department of Pediatrics, Quanzhou First Hospital, No. 248-252 East Street, Licheng District, Quanzhou 362000, Fujian Province, China.
Received: November 23, 2020
Peer-review started: November 23, 2020
First decision: December 8, 2020
Revised: December 10, 2020
Accepted: December 24, 2020
Article in press: December 24, 2020
Published online: March 6, 2021
Research background

Dwarfism is one of the most common diseases in the endocrine system of children. It is a complex process involving multiple genes and multiple factors. Genetic factors are the main factors affecting individual height differences, and the heritability of human height accounts for approximately 80%. The mechanism has not yet been clarified.

Research motivation

The rapid development of emerging technologies has resulted in increased understanding of on the related molecular etiological mechanisms. Some unexplained cases of short stature can be clarified by studying their genetic background by using related genetic testing methods. Efficient and highly sensitive diagnosis methods have become the focus of dwarfism research.

Research objectives

To analyze retrospectively the genetic variation by using a constructed panel related to dwarfism through next-generation sequencing platform sequencing analysis in order to screen candidate-related gene mutations that may clarify the molecular cause and provide a scientific basis for clinical treatment.

Research methods

Data from 39 dwarf patients in Quanzhou First Hospital were collected according to the inclusion and exclusion criteria, then the clinical examination, growth hormone drug challenge test, serum insulin-like growth factor-1 (IGF-1) and IGF binding protein 3 (IGFBP3) levels, other related tests, imaging examination, and chromosome karyotyping were analyzed. Next-generation sequencing was also performed to analyze the pathogenicity variability.

Research results

Of the 39 dwarfism patients, 10 had pathogenicity variability. Gene variation was found in the OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes. Of the 10 patients with pathogenicity variability, the related physical characteristics included double breast development and growth hormone deficiency, enuresis and indirect inguinal hernia on the left, two finger distance of 70.2 cm, head circumference of 49.2 cm, ischium/lower body length of 1.8 cm, weak limb muscles, and partial growth hormone deficiency. After 6 mo of growth hormone therapy, the concentrations of IGF-1 and IGF binding protein 3 increased from 215.2 ± 170.3 to 285.0 ± 166.0 and 3.9 ± 1.4 to 4.2 ± 1.1, respectively.

Research conclusions

Pathogenicity variability in the OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes was screened, and it may be related to dwarfism incidence.

Research perspectives

This study adds to the evidence-base and will clarify the molecular cause of dwarf diseases; however, larger sample size and multi-center studies are still needed in the future.