Objective To conduct a comprehensive analysis of the clinical and genetic characteristics associated with an undetermined cause-induced mixed developmental disorder case,aiming to establish a robust theoretical foundation for understanding the etiology of the child,facilitating genetic counseling,and guiding family reproduction.Methods The medi-cal and family history of the patient who presented to the Children's Rehabilitation Department of Maternal and Child Health Care Hospital of Longhua District in Shenzhen on January,2023,due to"inability to speak at the age of 3 years and 3 months,poor active social interaction,and small head circumference"were collected,followed by a comprehensive clinical examina-tion.Peripheral blood G-banding karyotype analysis was performed on both the children and their parents.Detection of FMR1 gene associated with Fragile X syndrome(FXS)was conducted in children.Whole exome sequencing(WES),Sanger se-quencing for pedigree verification of candidate variants,as well as bioinformatics software utilization to assess pathogenicity according to relevant guidelines from the American Society for Medical Genetics and Genomics(ACMG).A review was con-ducted on the clinical and genetic characteristics of Renpenning syndrome caused by PQBP1 variation.Results The G-banded karyotype analysis revealed no abnormalities in both the children and their parents.No abnormal amplification of FXS-related gene FMR1 was detected either.WES indicated that the patients carried PQBP1 hemizygous variation:C.586C＞T(p.Arg196Ter),leading to amino acid No.196 changing from arginine to a stop codon.Which was classified as"pathogenic mutation"based on ACMG Classification Standards and Guidelines for Genetic Variation.So far,16 types of PQBP1 mutation have been reported,and no case caused by c.586C＞T mutation has been reported in China.Different mutation types usually have different phenotypes.Conclusion Whole exome sequencing revealed that this case of mixed global growth retardation is caused by Renpenning syndrome caused by c.586C＞T mutation of PQBP1 gene.The present study has enhanced the clinical comprehension of the disease,thus holding significant guiding implications for the rational evaluation of children's prognosis and family planning.
PQBP1 geneRenpenning syndromemixed global growth retardationwhole exome sequencing
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