Detection Of SHOX Gene And Analysis Of Anthropometric Characteristics In 11 Children With Idiopathic Short Stature Of Yi Nationality

Objectives:To explore the abnormality of SHOX gene and SHOX gene abnormality in idiopathic short stature(idiopathicshortstature,ISS)of Yi nationality in Honghe Hani Yi Autonomous Prefecture of Yunnan Province by Sanger sequencing and MLPA method.At the same time,anthropometric indexes were analyzed to explore the relationship between clinical phenotype and genotype,so as to provide theoretical basis for the diagnosis and treatment of idiopathic short stature of ethnic minorities.Methods:Eleven right-handed children aged 4-12 years old from Honghe Hani and Yi Autonomous Prefecture in Yunnan Province from October 2019 to October 2020 were selected as subjects.Their height,weight,sitting height,upper arm length,forearm length,finger distance and leg length were measured,and DNA was extracted.SHOX gene and its exons,partial introns and CNEs were detected by Sanger and MLPA sequencing,in which MLPA verified the deletion and repetition of SHOX gene fragments,Sanger sequencing detected the possible base mutation of SHOX gene,and compared the results with GeneBandSHOX sequences.at the same time,the correlation between finger distance/sitting height and lower limb length/sitting height,genetic target height and bone age delay time was analyzed by Person..Results:In this study,a total of 11 children with idiopathic dwarf of Yi nationality were collected,including 7 girls(63.6%)and 4 boys(36.4%).SHOX gene mutations were detected in all 11 children by Sanger sequencing,including 1 intron homozygous mutation and other mutations were conservative non-coding DNA base mutations;Anthropometric indexes showed that the ratio of forearm length/height,upper arm length/height and arm span/height in children with ISS of Yi nationality was lower than that of Han idiopathic short stature in China,while there was no significant difference in height/sitting height,limb/trunk ratio,corrected height and limb/trunk ratio between Yi and Han idiopathic short stature in China.No deletion or repetition of SHOX gene fragment was detected by MLPA quantitative sequencing.Only Exon8 of ARSF gene,Exon6 of PRKX gene,Intronl of NLGN4X gene,Exon10 of ANOS1 gene,Exon 10 of FANCB gene and Exon 15 deletion mutation of AIFM1 gene were detected in the downstream PAR1 region of SHOX gene in 4 children.Exon5 copy number of PPP2R3B gene was increased in 1 patient and there was repetitive mutation.Conclusions:1.Compared with children with ISS of Han nationality,children with ISS of Yi nationality also have clinical phenotypes,such as shortening of upper limbs,long torso,decrease of trunk ratio of limbs and so on.2.Compared with Han idiopathic short stature children,SHOX gene fragment deletion and repetition were not found in Yi children with ISS,but mainly in the downstream regulatory sequence of SHOX gene.It is speculated that the base mutation of downstream regulatory sequence of SHOX gene may be related to the occurrence of ISS in Yi nationality.3.Due to the small number of samples in this study,whether the clinical phenotypes such as upper limb shortening in Yi children with ISS are related to base mutations in the downstream regulatory sequence of SHOX gene,it is necessary to expand the sample size and verify the gene function if necessary.