Study on pathogenic genes of dwarfism disease by next-generation sequencing

Abstract

BACKGROUND There are many factors that lead to dwarfism, and the mechanism has not yet been elucidated. Next-generation sequencing may identify candidate-related gene mutations, which may clarify the molecular cause. AIM To analyze genetic variation by using a constructed panel related to dwarfism by utilizing next-generation sequencing platform sequencing analysis to screen candidate-related gene mutations. METHODS Physical and laboratory characteristics, including clinical examination, growth hormone drug challenge test, serum insulin-like growth factor-1 (IGF-1), IGF binding protein 3, other related tests, imaging examination, and chromosome karyotyping, were analyzed. Next-generation sequencing was performed to analyze pathogenicity variability. RESULTS In 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. CONCLUSION OBSL1 , SLC26A2 , PTPN11 , COL27AI , HDAC6 , CUL7 , FGFR3 , DYNC2H1 , GH1 , and ATP7B genes may be related to the incidence of dwarfism, and more research needs to be performed to elucidate the mechanism.

Genomic adaptation of Ethiopian indigenous cattle to high altitude

“…SLC26A2 is a ubiquitously expressed SO4 2− transporter with high expression levels in cartilage and several epithelia (Ohana et al, 2012;Park et al, 2014). This gene is involved in body size and male fertility in humans (Kujala et al, 2007;Touré, 2019), and its mutations have been implicated in dwarfism (Yang and Liang, 2021) and dysplasia (Pineda et al, 2013;Zheng et al, 2019;Heidari et al, 2021).…”

“…The function of this gene is related to ion transport, and it plays a role in chondrocyte proliferation, differentiation, and growth in endochondral bone formation (Park et al, 2014). In humans, it regulates body size, and its recessive allele contributes to the dwarfism phenotype (Yang and Liang, 2021) and dysplasia (Pineda et al, 2013;Zheng et al, 2019;Heidari et al, 2021). A previous study reported a dominant allele at SLC26A2 linked to higher heels and stronger claws in dairy cattle, while mutation at the gene causes dysplasia (Brenig et al, 2003).…”