Published online Mar 6, 2021. doi: 10.12998/wjcc.v9.i7.1600
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
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.
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.
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.
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.
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.
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.
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.