de Vries D D, Buzing C J, Ruitenbeek W, van der Wouw M P, Sperl W, Sengers R C, Trijbels J M, van Oost B A
Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
Neuromuscul Disord. 1992;2(3):185-95. doi: 10.1016/0960-8966(92)90005-q.
A patient with the Pearson marrow and pancreas syndrome is presented. She showed an anaemia with neutropenia and thrombopenia, failure to thrive, diarrhoea, disturbed glucose homeostasis and lactic acidosis. An exocrine pancreatic insufficiency was lacking. The disease followed a fatal course. Biochemical investigations of skeletal muscle revealed a disturbed mitochondrial energy metabolism, while many ultrastructural abnormal features were observed in the muscle tissue. Molecular genetic studies showed a de novo deletion in the mitochondrial DNA (mtDNA), different in size from the already published deletions and flanked by two 4 bp direct repeats, interspaced by 4-5 non-repeated nucleotides. mtDNA from 12 other tissues showed the same deletion in different percentages. No obvious relation between these percentages and tissue dysfunction was found. In spite of an open reading frame of 74 codons, only little transcription product of the genomic region resulting from the deletion was found.
本文报告了一名患有皮尔逊骨髓和胰腺综合征的患者。她表现出贫血伴中性粒细胞减少和血小板减少、生长发育迟缓、腹泻、葡萄糖稳态紊乱和乳酸酸中毒。不存在外分泌性胰腺功能不全。该疾病呈致命病程。骨骼肌的生化检查显示线粒体能量代谢紊乱，同时在肌肉组织中观察到许多超微结构异常特征。分子遗传学研究显示线粒体DNA（mtDNA）发生了新发缺失，其大小与已发表的缺失不同，两侧为两个4 bp的直接重复序列，中间间隔4 - 5个非重复核苷酸。来自其他12个组织的mtDNA显示出相同的缺失，但比例不同。未发现这些比例与组织功能障碍之间存在明显关联。尽管缺失导致的基因组区域有一个74个密码子的开放阅读框，但仅发现了少量该区域的转录产物。
