猫叫综合征的临床与分子细胞遗传学研究

发布时间：2018-06-20 12:40

本文选题：猫叫综合征 + 核型分析　；参考：《中南大学》2012年硕士论文

【摘要】：目的：猫叫综合征(Cri-du-Chat syndrome, CDCS, MIM123450)是由于5号染色体短臂部分缺失所致的染色体缺失综合征,又称为5p部分单体综合征,是最常见的染色体缺失综合征之一。典型的CDCS患者的临床表型包括出生后单调的猫叫样哭声、满月脸、宽眼距、低耳位、小下颌、高额弓、低出生体重、严重的智力落后、肌张力低等,并可能伴有先天性心脏病、牙齿异常等多种复杂的表型。CDCS的核型亦有多种类型,可以分为新发生的5p末端缺失或者中间缺失,或者源于父母的平衡易位,还有部分为罕见的复杂异常。临床表型的复杂性及核型的多样性,使得人们对于CDCS的认识尚不清楚,对于CDCS的预防策略没有明确的方式。为了提高对CDCS的认识及诊断和预防水平,本研究收集了17个CDCS家系,应用分子细胞遗传学技术确诊CDCS患者的核型,并对其中9个患者进行了芯片检测,探讨染色体缺失区域大小与临床表型的关系,为克隆断裂位点、分析5p微缺失的分子机制打下基础。同时回顾性分析患者母亲妊娠时的情况,探究常规的监测能否预警妊娠CDCS,结合产前诊断技术,分析CDCS的复发风险。方法：对17个CDCS患者及其父母进行G-显带核型分析。应用猫叫综合征关键区基因位点特异性探针、Tel5p/5q探针进行荧光原位杂交(fluorescence in situ hybridization, FISH)检测患者及其父母。用SNP-Array(single nucleotide polymorphism-based arrays, SNP-Array)技术对9个患者进行全基因组DNA进行扫描分析。回顾分析17个家庭在妊娠猫叫综合征胎儿时的妊娠情况。对6个曾经生育过CDCS患者的孕妇,应用羊膜腔穿刺获取羊水细胞培养进行宫内产前诊断。结果：核型分析发现13个患者为单纯的5号染色体短臂末端缺失;2个患者携带一条源于5p和18p易位而来衍生的5号染色体；1个患者携带一条源于5p和11q易位而来衍生的5号染色体；1个患者发生同一条5号染色体末端缺失和臂间倒位。在这17例CDCS中,15例为新发生的突变,2例为母源的相互易位,未见中间缺失的CDCS患者。SNP芯片检测的9例CDCS缺失长度不一,其中1例有新发生的18号染色体短臂部分重复,该变异由于片段较小而没有被G显带技术检测出。对这17例猫叫综合征病历进行回顾分析,胎儿期母血产前筛查指标未见异常,产检除胎儿宫内发育受限外亦未见其他特异性指征。夫妻核型均正常的4个家庭再孕时,羊水细胞培养结果显示4个胎儿核型均正常；2个易位携带者家庭再孕时,羊水产前诊断显示1例为母源的平衡易位携带者,1例携带母源的衍生的5号染色体,其胎儿出生后将成为CDCS患者结论：确诊了17个家系中CDCS患者的核型,发现了一例新发生的5p部分单体合并隐匿18p微小重复患者,确诊了一例以往的技术中无法确诊的5号染色体倒位合并5p末端缺失患者的核型。通过高分辨率的SNP-array技术,将临床表型与染色体核型的关系联系起来。家庭中新发生的CDCS患者,其复发CDCS的风险低,可选择自然妊娠后产前诊断；而当双亲之一为平衡易位携带者时,复发风险高,可考虑PGD方式助孕。
[Abstract]:Objective : To investigate the clinical phenotype of CDCS ( CDCS ) in the diagnosis and prevention of CDCS .

Methods : 17 CDCS patients and their parents were analyzed by G - banding . Fluorescence in situ hybridization ( FISH ) was used to detect the pregnancy in 9 patients .

Results : The karyotype analysis showed that 13 patients were short - arm short - arm deletion of 5 chromosome ; 2 patients carry a chromosome 5 derived from the translocation of 5p and 18p ;
One patient carries a chromosome 5 derived from translocation of 5p and 11q ;
In the 17 cases of CDCS , 15 cases were newly - occurring mutations , 2 cases were isolated from the mother - source , 2 cases were not detected by G - banding technique . Among them , 1 case had a new 18 - chromosome short - arm part which was not detected by G banding technique .
The prenatal diagnosis of amniotic fluid showed that 1 case was a balanced translocation carrier of maternal source , 1 case with mother source derived 5 chromosome , and its fetus will become a CDCS patient .

Conclusion : The nuclear type of CDCS patients in 17 families has been confirmed . A new 5p partial monomer combined with 18p microreplicated patients has been identified . A case of nuclear type with 5 p - terminal deletions confirmed by the previous technique has been confirmed . By means of high resolution SNP - array technique , the relationship between clinical phenotype and chromosome karyotype is associated . The risk of CDCS in the family is low , and the prenatal diagnosis can be selected after spontaneous pregnancy .
When one of the parents is the balanced translocation carrier , the risk of recurrence is high , and the PGD method can be taken into consideration .
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R722.11

【相似文献】