产前诊断CPLANE1基因新发变异所致Joubert综合征一例

Prenatal diagnosis of Joubert syndrome caused by de novo mutations of CPLANE1 gene

本文报告了一例超声提示胎儿小脑蚓部发育不良的产前诊断病例。该孕妇27岁,孕20周+6超声发现胎儿小脑下蚓部部分分离(Dandy-Walker变异型),上下唇不能闭合、多指(趾),初步诊断为胎儿多发畸形。羊水染色体核型及染色体微阵列分析未见异常。经过遗传咨询和深入沟通,再次行胎儿羊膜腔穿刺行全外显子组测序检测,结果提示胎儿CPLANE1基因第19号外显子和第17号外显子分别存在c.3435G>A(p.W1145X)和c.2941C>G(p.p981A)复合杂合变异,分别遗传自父亲和母亲,且上述变异位点均未见文献报道,诊断为Joubert综合征。孕妇及家属考虑到胎儿除有面部和肢体发育畸形外,出现神经系统异常的风险极大,最终选择引产。

We report a case of fetal cerebellar vermis dysplasia diagnosed prenatally by ultrasonography.Ultrasonography of the 27-year-old woman at 20+6 gestational weeks revealed partial separation of the cerebellar vermis(Dandy-Walker variants),unclosable upper and lower lips,and polydactyly,based on which a preliminary diagnosis of multiple fetal malformations was made.Karyotype and chromosomal microarray(CMA)analysis of the amniotic fluid showed no abnormality.After genetic counseling,amniocentesis was performed again for a whole-exome sequencing test.The results suggested that there are compound heterozygous variations of c.3435G>A(P.W1145X)and c.2941C>G(p.p981A)in the exon 19 and exon 17 of the CPLANE1 gene,which were both de novo mutations and inherited from the father and mother,respectively.The fetus was diagnosed as Joubert syndrome.Given the facial and limb deformities and a significant risk of neurological abnormalities of the fetus,the patient and her family decided to terminate the pregnancy.