Herring W J, Litwer S, Weber J L, Danner D J
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA.
Am J Hum Genet. 1991 Feb;48(2):342-50.
Maple syrup urine disease in humans results from inherited defects in branched chain alpha-ketoacid dehydrogenase, a mitochondrial multienzyme complex. A variety of genetic changes may produce this phenotype by affecting the function of any of the three complex-specific subunits. The varied clinical expression observed in patients may be partially explained by the defects in the involved subunit. Here we report localization of the gene for the branched chain acyltransferase component of the complex to human chromosome 1 and describe a proband who is a compound heterozygote at this locus. One allele, inherited from the father, produces transcripts with 124 nucleotides deleted from the coding region. The deletion is not found in the branched chain acyltransferase gene, implying that the deleted transcripts arise by an error in transcript processing. Cells from the patient's mother contain 50% of the normal amount of mRNA for the subunit, and the proband has inherited this nonexpressing allele from her. As a result, the proband produces no acyltransferase protein and therefore has greatly impaired complex activity. A phenotypically normal sibling is shown to be genetically similar to the mother having inherited the mother's nonexpressing allele and the father's normal allele.
人类枫糖尿症是由线粒体多酶复合物支链α-酮酸脱氢酶的遗传性缺陷引起的。多种基因变化可能通过影响三种复合物特异性亚基中任何一种的功能而产生这种表型。患者中观察到的不同临床表型可能部分由所涉及亚基的缺陷来解释。在此，我们报告该复合物的支链酰基转移酶成分的基因定位于人类染色体1，并描述了一位在该位点为复合杂合子的先证者。从父亲遗传的一个等位基因产生的转录本在编码区缺失了124个核苷酸。在支链酰基转移酶基因中未发现该缺失，这意味着缺失的转录本是由转录加工错误产生的。患者母亲的细胞中该亚基的mRNA含量为正常量的50%，先证者从她那里继承了这个不表达的等位基因。因此，先证者不产生酰基转移酶蛋白，从而复合物活性严重受损。一名表型正常的同胞在遗传上与母亲相似，继承了母亲的不表达等位基因和父亲的正常等位基因。
