两个18号染色体臂间倒位家系的产前诊断与遗传咨询

Prenatal diagnosis and genetic counseling for two pedigrees with pericentric inversion of chromosome 18

目的了解超声及实验室检查,以及不同遗传诊断技术在筛查及明确源于亲代臂间倒位的18号染色体重组胎儿中的作用,探讨18号染色体重组胎儿表型与其核型之间的关联。方法分析分别于2017年3月及2018年3月在厦门市妇幼保健院接受产前诊断及遗产咨询的2个18号染色体臂间倒位家系的胎儿及其父母染色体核型、染色体微阵列分析及荧光原位杂交等检查结果。并检索科学引文索引、PubMed、中国知网中国全文数据库、万方数据等数据库,检索时间为1970年至2018年6月。对本文及文献报道的18号染色体臂间倒位产前诊断家系孕产妇的遗传咨询、超声及实验室检查发现、妊娠结局及随访等情况进行分析。结果家系1孕22周孕妇外院行无创产前检测(non-invasive prenatal testing,NIPT)提示胎儿18号染色体非整倍体高风险;孕24周^+2本院超声提示胎儿存在室间隔缺损、小下颌等,经产前诊断确认胎儿染色体核型为46,XY,rec(18)dup(18q)inv(18)(p11.32q12.1)pat,系遗传自父亲;胎儿父亲18号染色体存在臂间倒位,核型为46,XY,inv(18)(p11.32q12.1)。家系2孕12周^+3血清学筛查提示胎儿18-三体高风险,孕13周^+3超声提示胎儿颈项透明层(nuchal translucency,NT)增厚、孕15周^+6双侧脉络丛囊肿,经产前诊断确认胎儿核型为46,XX,rec(18)dup(18q)inv(18)(p11.32q12.1)mat,系遗传自母亲;母亲系18号染色体臂间倒位携带者,核型为46,XX,inv(18)(p11.32q12.1)。共检索到5个18号染色体臂间倒位家系的文献报道,结合本文2个家系共9例18号染色体重组胎儿,其中3个18号染色体臂间倒位家系的孕妇血清学筛查或NIPT提示18-三体高风险;7例胎儿存在超声软指标或结构异常。结论超声筛查对于18号染色体重组胎儿的发现具有较高的检出率,但超声表型与其核型之间的关联尚不明确;染色体微阵列分析及荧光原位杂交等方法的联合运用,有助于明确复杂衍生染色体的类型及其来源。

Objective To investigate the roles of ultrasound, laboratory methods, and genetic diagnostic techniques in screening and diagnosing fetuses with an unbalanced recombination of chromosome 18[rec( 18)] due to parental pericentric inversion, and the relationship between rec( 18) fetal phenotypes and their recombinant chromosomes. Methods We analyzed two pedigrees with pericentric inversion of chromosome 18 (including the fetuses and their parenls) which received prenatal diagnosis and genetic counseling on March 2017 and March 2018 respectively at Xiamen Maternity and Children Health Care Hospital through karyotype analysis, chromosome microarray analysis(CMA) and fluorescence in situ hybridization (FISH). Literatures were retrieved from Scientific Citation Index. PubMed. China National Knowledge Infrastructure(CNKl) and Wan fang Data from 1970 to June 2018. The genetic counseling records, ultrasound and laboratory findings, pregnancy outcomes of families with pericentric inversion of chromosome 18 in this study and the included literatures were reported and analyzed. Results Non-invasive prenatal testing (NIPT) of one case indicated high risk of fetal trisomy 18 at 22 weeks of gestation. And the imaging exami nation indicated that fetus had interventricular septal defect and micrognathia at 24^+2 weeks. Prenatal diagnosis confirmed that the fetal karyotype was 46,XY,rec( 18)dup( 18q) inv(18)(pl 1.32q 12.1) pat, which was originated from his father whose karyotype was 46,XY,inv( 18)(pl 1.32q 12.1). In the other case, serum screening testing indicated high risk of fetal trisomy 18 at 12^+3 weeks. Imaging examination indicated that fetus had thickened nuchal translucency at 13^+3 weeks and bilateral choroid plexus cysts at 15^+6 weeks. Prenatal diagnosis confirmed that the fetal karyotype was 46.XY.rec( 18)dup( 18q)inv( 18)(pl 1.32ql2.1) mat. which was originated from his mother whose karyotype was 46,XX,inv(18)(pl 1.32ql2.1). Amo ng the nine fetuses, including seven from five pedigrees reported in the literature retrieved and two from the two pedigrees we reported, seven showed abnormal soft markers or structures in ultrasound and three of the seven pedigrees had high risk of fetal trisomy 18. Conclusions Ultrasound screening is highly sensitive in detecting rec(18) fetuses, yet the association between ultrasound features and fetal karyotypes is not clear. The combination of multiple genetic analysis methods, including karyotype analysis, CMA and FISH, may be conducive to clarifying the types and sources of complex derived chromosomes.