Multiple mitochondrial DNA deletions and persistent hyperthermia in a patient with Brachmann-de Lange phenotype

• Published in: American journal of medical genetics Vol. 65; no. 1; pp. 82 - 88
• Main Authors: Melegh, Béla, Bock, Ildikó, Gáti, István, Méhes, Károlu
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 02-10-1996; Wiley-Liss
• Subjects: Biological and medical sciences; Blotting, Southern; Brachmann-de Lange syndrome; Complex syndromes; De Lange Syndrome - genetics; De Lange Syndrome - pathology; DNA, Mitochondrial - genetics; Fatal Outcome; fever; Fever - genetics; Humans; hyperthermia; Infant, Newborn; Male; Medical genetics; Medical sciences; mitochondrial DNA deletions; Muscle, Skeletal - ultrastructure; Polymerase Chain Reaction; Sequence Deletion; thermoregulation; Human; Nervous system diseases; De Lange syndrome; Genetic inheritance; Diseases of the osteoarticular system; Infant; Mitochondrial DNA; Striated muscle; Genetic disease; Case study; Pathology; Association; Malformation; Deletion; Genetics; Complex syndrome; Hyperthermia
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/(SICI)1096-8628(19961002)65:1<82::AID-AJMG13>3.0.CO;2-N

In a newborn boy with characteristics of Brachmann‐de Lange syndrome (BDLS) high temperatures were observed on the second day after birth and recurred 2‐6 times daily during the 7 months of the patient's life. After transient hypertonia hypotonia developed. In muscle biopsy specimen taken on the 51st day of life, serious and progressive distortion of mitochondria was observed. In several mitochondria the cristae structure was broken, other mitochondria were shrunken and the damage progressed towards further deterioration in other organelles. At several points between the myofibrils amorphous material was seen possible debris of destroyed mitochondria. Most myofibrils seemed to be intact; however, in some areas myolytic signs were present. Analysis of the mitochondrial DNA (mtDNA) showed multiple deletions in skeletal and heart muscles, liver, lung and kidney. Since the mtDNA encodes several proteins of the respiratory complexes, the deleted mtDNA certainly affected the integrity of the mitochondrial oxidative phosphorylation process by synthesis of abnormal proteins. In the present case the hyperthermia may have been a result of the mtDNA damage. © 1996 Wiley‐Liss, Inc.