Somatic GNA11/GNAQ variants in a cohort of Chinese children with phakomatosis pigmentovascularis  

作　　者：Bin Zhang Rui He Riga Wu Zhou Yang Man Hu Nan Zhang Wu Guo Zigang Xu Lin Ma 

机构地区：[1]Department of Dermatology,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing,China [2]Department of Dermatology,Zhengzhou University,Affiliated Children’s Hospital,Henan Children’s Hospital,Zhengzhou Children’s Hospital,Zhengzhou,China [3]Department of Dermatology,Affiliated Hospital of Inner Mongolia Medical University,Hohhot,China [4]Department of Ophthalmology,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing,China [5]Department of Pathology,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing,China

出　　处：《Pediatric Investigation》2024年第2期117-125,共9页儿科学研究（英文）

基　　金：Beijing Natural Science Foundation:Grant/Award Number:7222058;The Open Project of Henan Clinical Research Center of Childhood Diseases:Grant/Award Number:YJZX202209;National Regional Medical Center Opening Project:Grant/Award Number:NRMC0101;Investigator Initiated Project:Grant/Award Number:[2022]-E-028-Y;BCH Young Investigator Program(BCHYIP):Grant/Award Number:3-1-014-01-36。

摘　　要：Importance:Postzygotic mutations in the GNAQ/GNA11 genes,which encode the G-protein nucleotide binding protein alpha subunits,have been identified in patients with phakomatosis pigmentovascularis(PPV).However,little is known about the Chinese population.Objective:To identify pathogenic mutations in pediatric patients with PPV within the Chinese population.Methods:We performed whole-exome sequencing(WES)using skin lesion tissues from pediatric patients diagnosed with PPV.Additionally,ultradeep-targeted sequencing was conducted to validate the somatic mutations.A genotype-phenotype correlation was analyzed by integrating data from previous reports with the findings of the present study.Results:Thirteen patients were enrolled,all diagnosed with the cesioflammea type of PPV,except for one patient with an unclassifiable type.We identified somatic GNA11 c.547C>T(p.R183C)variant in seven patients and GNAQ c.548G>A(p.R183Q)in four patients,with low allelic fractions ranging from 2.1%to 8.6%through ultradeep sequencing.Besides,a GNAQ c.548G>A(p.R183Q)variant was detected through targeted sequencing in one of two patients who did not exhibit detectable variants via WES.The genotype-phenotype correlation analysis,involving 15 patients with a GNA11 variant and 10 with a GNAQ variant,revealed that facial capillary malformation(87%vs.50%,P=0.075)and ocular melanocytosis(80%vs.40%,P=0.087)appeared to be more frequent in patients with GNA11 mutation compared to those with GNAQ mutations.All four patients diagnosed with cesiomarmorata type or overlapping cesioflammea and cesiomarmorata type PPV carried the GNA11 variant.Interpretation:Our study demonstrated that the majority of PPV patients in the Chinese population carried a postzygotic variant of GNAQ/GNA11,thus further confirming the pathogenic role of GNAQ/GNA11 mosaicism in the development of PPV cesioflammea type.

关 键 词：Phakomatosis pigmentovascularis GNA11 GNAQ Somatic variant 

分 类 号：R726.5[医药卫生—儿科]