PDF(Pubmed)
Abstract：
Achondroplasia 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.
A 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.
We 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.
A 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.
We 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.
摘要：
软骨发育不全是由FGFR3基因错义变异引起的先天性骨骼系统畸形，发生率为每20,000-30,000新生儿中1例，这是一种常染色体显性遗传疾病。尽管成像特征相似,纯合子软骨发育不全是绝对致命的，而杂合子软骨发育不全不会导致胎儿死亡。
在妊娠中期，通过产前超声检查发现胎儿具有进行性根茎性短肢和明显狭窄的胸部。羊水样本的基因测序结果表明罕见的错义变异NM_000142.4：c.1123G>T（p。Gly375Cys)，导致甘氨酸被半胱氨酸取代。重新测序证实它是一个杂合变体，然后通过放射学检查在尸体中确认胸廓狭窄。
我们确定了FGFR3基因的杂合变体是胎儿严重软骨发育不全的罕见致病变体。p.Gly375Cys的杂合变体可具有类似于纯合子的严重表型。产前超声检查与基因检查相结合对鉴别杂合性软骨发育不全和纯合性软骨发育不全至关重要。FGFR3基因的p.Gly375Cys变体可能是诊断严重软骨发育不全的重要靶标。
在妊娠中期，通过产前超声检查发现胎儿具有进行性根茎性短肢和明显狭窄的胸部。羊水样本的基因测序结果表明罕见的错义变异NM_000142.4：c.1123G>T（p。Gly375Cys)，导致甘氨酸被半胱氨酸取代。重新测序证实它是一个杂合变体，然后通过放射学检查在尸体中确认胸廓狭窄。
我们确定了FGFR3基因的杂合变体是胎儿严重软骨发育不全的罕见致病变体。p.Gly375Cys的杂合变体可具有类似于纯合子的严重表型。产前超声检查与基因检查相结合对鉴别杂合性软骨发育不全和纯合性软骨发育不全至关重要。FGFR3基因的p.Gly375Cys变体可能是诊断严重软骨发育不全的重要靶标。
