Unequal interchromosomal rearrangements may result in elastin gene deletions causing the Williams-Beuren syndrome
Unequal interchromosomal rearrangements may result in elastin gene deletions causing the Williams-Beuren syndrome
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DOI：
10.1093/hmg/5.12.1893
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发表时间：
1996-12-01
影响因子：
3.5
通讯作者：
Schinzel, A
中科院分区：
文献类型：
--
作者：
Dutly, F;Schinzel, A
Williams-Beuren综合征（WBS）通常是7q11.23处的间质微缺失的结果，其包括弹性蛋白基因，从而导致弹性蛋白基因位点处的半合子性。许多作者已经报道缺失的起源类似于60%的病例是母亲的，40%的病例是父亲的，在WBS患者及其父母中，对位于微缺失区侧翼的祖父母标记进行的分离分析表明，在大多数情况下，祖父母和祖父母7号染色体之间的重组发生在缺失发生在缺失染色体来源的亲本减数分裂期间，因此，大多数缺失被认为是同源染色体7之间不平等交换的结果（染色体间重排），而在其余情况下，染色体内重组（在一条染色体7的染色单体之间）可能已经发生，这些结果表明，大多数弹性蛋白基因区域的间质缺失发生在减数分裂期间，由于不平衡重组，而少数可能发生在减数分裂之前或期间，可能是由于染色体内重排，先证者的同胞与未受影响的父母的染色体间重排的复发风险必须是可以忽略不计的，这与几乎所有WBS病例的零星发生的观察非常吻合。
Williams-Beuren syndrome (WBS) is generally the consequence of an interstitial microdeletion at 7q11.23, which includes the elastin gene, thus causing hemizygosity at the elastin gene locus, The origin of the deletion has been reported by many authors to be maternal in similar to 60% and paternal in 40% of cases, Segregation analysis of grandparental markers flanking the microdeletion region in WBS patients and their parents indicated that in the majority of cases a recombination between grandmaternal and grandpaternal chromosomes 7 at the site of the deletion had occurred during meiosis in the parent from whom the deleted chromosome stemmed, Thus, the majority of deletions were considered a consequence of unequal crossing-over between homologous chromosomes 7 (interchromosomal rearrangement) while in the remaining cases an intrachromosomal recombination (between the chromatids of one chromosome 7) may have occurred, These results suggest that the majority of interstitial deletions of the elastin gene region occur during meiosis, due to unbalanced recombination while a minority could occur before or during meiosis probably due to intrachromosomal rearrangements, The recurrence risk of the interchromosomal rearrangements for sibs of a proband with non-affected parents must be negligible, which fits well with the observation of sporadic occurrence of almost all cases of WBS.