Heterozygous variant in FGFR3 underlying severe phenotypes in the second trimester: a case report

作者全名："Chen, Shujun; Dong, Hongmei; Luo, Yong; Zhang, Yingpin; Li, Pan"

作者地址："[Chen, Shujun; Luo, Yong; Zhang, Yingpin] First Peoples Hosp, Chongqing Liang Jiang New Area, Dept Ultrasound, Chongqing 400010, Peoples R China; [Chen, Shujun; Dong, Hongmei; Li, Pan] Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, Chongqing 400010, Peoples R China; [Chen, Shujun; Dong, Hongmei; Li, Pan] Chongqing Med Univ, Inst Ultrasound Imaging, Chongqing 400010, Peoples R China; [Dong, Hongmei] Women & Childrens Hosp Chongqing Med Univ, Chongqing Hlth Ctr Women & Children, Dept Ultrasound, Chongqing 400010, Peoples R China"

通信作者："Li, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, Chongqing 400010, Peoples R China.; Li, P (通讯作者)，Chongqing Med Univ, Inst Ultrasound Imaging, Chongqing 400010, Peoples R China."

来源：BMC MEDICAL GENOMICS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000971016300001

JCR分区：Q3

影响因子：2.1

年份：2023

卷号：16

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Achondroplasia; FGFR3 gene; Heterozygous; Rare variant; Severe phenotype

摘要："BackgroundAchondroplasia is a congenital skeletal system malformation caused by missense variant of FGFR3 gene with an incidence of 1 per 20,000-30,000 newborns, which is an autosomal dominant inheritance disease. Despite similar imaging features, the homozygous achondroplasia is absolutely lethal due to thoracic stenosis, whereas heterozygous achondroplasia does not lead to fetal death.Case presentationA fetus with progressive rhizomelic short limbs and overt narrow chest was detected by prenatal ultrasound in the second trimester. Gene sequencing results of amniotic fluid sample indicated a rare missense variant NM_000142.4: c.1123G > T(p.Gly375Cys), leading to a glycine to cysteine substitution. Re-sequencing confirmed that it was a heterozygous variant, and thoracic stenosis was then confirmed in the corpse by radiological examination.ConclusionsWe identified a heterozygous variant of the FGFR3 gene as the rare pathogenic variant of severe achondroplasia in a fetus. Heterozygous variants of p.Gly375Cys may have a severe phenotype similar to homozygote. It's crucial to combine prenatal ultrasound with genetic examination to differentiate heterozygous from homozygous achondroplasia. The p.Gly375Cys variant of FGFR3 gene may serve as a vital target for the diagnosis of severe achondroplasia."

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