单亲二倍体(uniparental disomy,UPD)是指在染色体核型中,某些同源染色体或染色体上的部分片段均来源于双亲中的一方,未检测到另一亲本来源的染色体或染色体的部分片段[1]。单亲本来源在法医学检案中可以表现为短串联重复(short tandem ...单亲二倍体(uniparental disomy,UPD)是指在染色体核型中,某些同源染色体或染色体上的部分片段均来源于双亲中的一方,未检测到另一亲本来源的染色体或染色体的部分片段[1]。单亲本来源在法医学检案中可以表现为短串联重复(short tandem repeat,STR),不符合孟德尔遗传定律。本研究通过2个家系不同染色体来源的单亲二倍体来展示这一现象对法医DNA检测产生的影响,希望给法医工作者提供参考。展开更多
Herlitz junctional epidermolysis bullosa (JEB) is an autosomal recessive mecha nobullous disorder that results from loss-of-function mutations in the genes e ncoding the basement membrane component, laminin 5. Typical...Herlitz junctional epidermolysis bullosa (JEB) is an autosomal recessive mecha nobullous disorder that results from loss-of-function mutations in the genes e ncoding the basement membrane component, laminin 5. Typically, there are framesh ift, splice site or nonsense mutations on both alleles of either theLAMA3,LAMB3o rLAMC2genes,withaffectedindividuals inheriting one mutated allele from each pare nt. In this report, we describe a patient with Herlitz JEB in whom DNA analysis revealed homozygosity for the recurrent nonsense mutation R635X in LAMB3, locate d on chromosome 1q32.2. However, screening of parental DNA showed that although the patient’s father was a heterozygous carrier of this mutation, the mother’s DNA showed only wild-type sequence. Subsequent genotype analysis using 13 micr osatellite markers spanning chromosome 1 revealed that the affected child was ho mozygous for the entire seriesofmarkerstestedandthatalloftheallelesoriginatedfro m the father. These results indicate that the Herlitz JEB phenotype in this pati ent is due to complete paternal isodisomy of chromosome 1 and reduction to homoz ygosity of the mutant LAMB3 gene locus. This is the fourth case of uniparental d isomy to be described in Herlitz JEB, but it represents the first example of com plete paternal isodisomy for chromosome 1 with a pathogenic mutation in the LAMB 3 gene. These findings have important implications for mutation screening in JEB and for genetic counselling.展开更多
文摘目的通过染色体微阵列分析(CMA)技术分析孩子的遗传背景,对母子间四个短串联重复序列(STR)STR位点不符合孟德尔遗传规律的亲子鉴定进行分析判断,给出鉴定意见。方法采用AGCU EX22和AGCU EX21+1多重荧光复合扩增分析系统检测D3S1358等39个STR位点。应用AGCU EX21+1-FS及AGCU EX 19X多重荧光复合扩增分析系统增加常染色体和X染色体遗传标记检测。应用染色体微阵列分析技术分析母子间出现四个STR位点不符合遗传规律的原因。结果经检测39个STR位点结果显示:孩子与被检母之间2号染色体上存在四个不符合遗传规律的STR位点。被检母:D2S441为11/11.3,TPOX为9/9,D2S1338为20/23,D2S1776为11/12。孩子:D2S441为10/10,TPOX为8/8,D2S1338为16/16,D2S1776为13/13,该4个STR基因型均为纯合子。而被检父均能提供孩子必需的等位基因。增加检测AGCU EX21+1-FS及AGCU EX 19X分析系统遗传标记后,孩子与被检母之间未再出现新的不符合基因位点,推测孩子2号染色体为单亲二倍体(UPD)。CMA结果表明除2号染色体外的常染色体的SNP信号都有3条带,说明其等位基因都有AA、AB、BB三种组合,符合孟德尔遗传规律。但2号染色体的SNP信号为两条带,且带的位置在2拷贝处,说明其拷贝数为2,等位基因只有AA和BB两种组合,即等位基因均为纯合状态,不符合孟德尔遗传规律。UPD-Tool软件分析整条2号染色体的纯合状态比例几乎达到100%,且与父亲基因型相同的比例明显高于母亲,为父源性UPD。结论在亲子鉴定中,当同一染色体上存在多个基因座不符合孟德尔遗传规律时,应考虑为单亲二倍体所致。同时,需进一步分析进行确认,以免造成误判。
文摘单亲二倍体(uniparental disomy,UPD)是指在染色体核型中,某些同源染色体或染色体上的部分片段均来源于双亲中的一方,未检测到另一亲本来源的染色体或染色体的部分片段[1]。单亲本来源在法医学检案中可以表现为短串联重复(short tandem repeat,STR),不符合孟德尔遗传定律。本研究通过2个家系不同染色体来源的单亲二倍体来展示这一现象对法医DNA检测产生的影响,希望给法医工作者提供参考。
文摘Herlitz junctional epidermolysis bullosa (JEB) is an autosomal recessive mecha nobullous disorder that results from loss-of-function mutations in the genes e ncoding the basement membrane component, laminin 5. Typically, there are framesh ift, splice site or nonsense mutations on both alleles of either theLAMA3,LAMB3o rLAMC2genes,withaffectedindividuals inheriting one mutated allele from each pare nt. In this report, we describe a patient with Herlitz JEB in whom DNA analysis revealed homozygosity for the recurrent nonsense mutation R635X in LAMB3, locate d on chromosome 1q32.2. However, screening of parental DNA showed that although the patient’s father was a heterozygous carrier of this mutation, the mother’s DNA showed only wild-type sequence. Subsequent genotype analysis using 13 micr osatellite markers spanning chromosome 1 revealed that the affected child was ho mozygous for the entire seriesofmarkerstestedandthatalloftheallelesoriginatedfro m the father. These results indicate that the Herlitz JEB phenotype in this pati ent is due to complete paternal isodisomy of chromosome 1 and reduction to homoz ygosity of the mutant LAMB3 gene locus. This is the fourth case of uniparental d isomy to be described in Herlitz JEB, but it represents the first example of com plete paternal isodisomy for chromosome 1 with a pathogenic mutation in the LAMB 3 gene. These findings have important implications for mutation screening in JEB and for genetic counselling.
