COL2A1基因突变所致先天性脊柱骨骺发育不良的产前分子诊断

Prenatal molecular diagnosis of two pregnancies in familial G504S mutation of COL2A1 gene resulting spondylepiphyseal dysplasia congenita

目的：对COL2A1基因（typeⅡcollagen gene）G504S突变导致的先天性脊柱骨骺发育不良（SEDC）家系的2例中期妊娠患者进行产前分子诊断。方法：分别对患者于19＋3孕周和18＋6孕周进行羊膜囊穿刺术抽取羊水，提取羊水脱落细胞DNA，对COL2A1基因的第23外显子扩增，对其产物测序。同时第1例胎儿从17＋3孕周～27＋3孕周、第2例胎儿从16＋1孕周～19＋1孕周对股骨长度进行B超动态检测。结果：COL2A1的23外显子测序结果显示第1例胎儿带有与母亲同样的COL2A1基因G504S突变。第2例胎儿COL2A1基因无突变。B超的追踪检测显示2例胎儿颅骨双顶径都与孕龄相符。第1例患病胎儿股骨增长随孕龄的增加而逐渐减慢，但孕23周前减慢不十分明显。病例2的胎儿股骨长度与孕龄相符，现继续妊娠观察。于第27＋5孕周对第1例患病胎儿行引产术后，影像学检测显示胎儿脊柱扁平、长骨明显短小，证实胎儿患有SEDC。结论：对于有SEDC风险的胎儿进行基因检测非常重要，可以在B超诊断前了解胎儿基因型并明确诊断。B超对胎儿股骨长度的动态检测有助于SEDC的诊断。

Objective To report the prenatal molecular diagnosis for two gravida in a family with spondylepiphyseal dysplasia congenita （SEDC） caused by G504S mutation of COL2A1 gene. Methods DNA of the two fetuses was extracted from amniotic fluid at the 19 ＋ 3 and 18 ＋ 6 weeks of gestation respectively. Direct sequencing of two samples were performed after amplifying exon 23 of COL2A1 containing the potential mutation. The femur length and biparietal diameter of the first fetus were measured by sonographic scans every two weeks from 17 ＋ 3 weeks to 27 ＋ 3 weeks of gestation ,and for the second fetus these parameters were measured from 16 ＋ 1 to 19 ＋ 1 weeks of gestation. Results Sequncing analysis revealed the first fetus and his mother presented the same mutation which is specifically associated with SEDC ,but the second fetus did not show the mutation of COL2A1 gene. Biparietal diameters of the both fetuses were appropriate for gestational age. Femur length of the second fetus was normal for gestational age but that of the first fetus was shortened evidently after the 23 week of gestation. The parents of the first fetus determined to terminate the pregnancy. A medical termination was carried out at 27 ＋ 5 weeks of gestation and a male fetus with a relatively large head and short limbs was delivered. The radiological findings of the fetus were consistent with SEDC including generalized platy spondesand shortened long bgnes. Conclusions Prenatal molecular diagnosis is important for the fetus with risk of SEDC and useful for genetic counseling. Genotype of fetus with risk of SEDC can be identified before sonographic scan. Molecular genetic analysis in conjunction with sonographic monitoring was helpful in prenatal diagnosis of SEDC.