Spotila L D, Sereda L, Prockop D J
Department of Biochemistry and Molecular Biology, Jefferson Institute of Molecular Medicine, Jefferson Medical College, Philadelphia 19107-6799.
Am J Hum Genet. 1992 Dec;51(6):1396-405.
Uniparental disomy for chromosome 7 has been described previously in two individuals with cystic fibrosis. Here, we describe a third case that was discovered because the proband was homozygous for a mutation in the COL1A2 gene for type I procollagen, although his mother was heterozygous and his father did not have the mutation. Phenotypically, the proband was similar to the two previously reported cases with uniparental disomy for chromosome 7, in that he was short in stature and growth retarded. Paternity was assessed with five polymorphic markers. Chromosome 7 inheritance in the proband was analyzed using 12 polymorphic markers distributed along the entire chromosome. Similar analysis of the proband's two brothers established the phase of the alleles at the various loci, assuming minimal recombination. The proband inherited only maternal alleles at five loci and was homozygous at all loci examined, except one. He was heterozygous for an RFLP at the IGBP-1 locus at 7p13-p12. The results suggest that the isodisomy was not complete because of a recombination event involving the proximal short arms of two maternal chromosomes. In addition, the phenotype of proportional dwarfism in the proband suggests imprinting of one or more growth-related genes on chromosome 7.
先前在两名囊性纤维化患者中描述过7号染色体单亲二体。在此，我们描述第三例病例，该病例是因为先证者在I型前胶原的COL1A2基因中一个突变位点呈纯合状态而被发现的，尽管其母亲是杂合子，而其父亲没有该突变。从表型上看，该先证者与先前报道的两例7号染色体单亲二体病例相似，即身材矮小且生长发育迟缓。用五个多态性标记评估亲子关系。使用沿整个染色体分布的12个多态性标记分析先证者的7号染色体遗传情况。对先证者的两个兄弟进行类似分析，假设重组最少，确定了各个位点上等位基因的相位。先证者在五个位点仅继承了母本等位基因，并且在所检测的所有位点上均为纯合子，但有一个位点除外。他在7p13 - p12的IGBP - 1位点的一个限制性片段长度多态性（RFLP）上是杂合的。结果表明，由于涉及两条母本染色体近端短臂的重组事件，等二体并不完全。此外，先证者成比例侏儒症的表型提示7号染色体上一个或多个与生长相关的基因存在印记现象。
