Journal ArticleDOI
Anticipation of autosomal dominant progressive external ophthalmoplegia with hypogonadism
Atle Melberg,Henrik Arnell,Niklas Dahl,Erik Stålberg,Raili Raininko,Anders Oldfors,Benjamin Bakall,Per Olov Lundberg,Elisabeth Holme +8 more
TLDR
It is hypothesized that the nuclear gene causing this enigmatic disorder may be directly influenced by an expansion of an unstable DNA sequence and that the resulting phenotype is caused by a concerted action with multiple deletions of mtDNA.Abstract:
A large Swedish family with members affected by progressive external ophthalmoplegia with hypogonadism were followed-up and reviewed. Hypogonadism included delayed sexual maturation, primary amenorrhea, early menopause, and testicular atrophy. Cataracts, cerebellar ataxia, neuropathy, hypoacusia, pes cavus, tremor, parkinsonism, depression, and mental retardation were other features observed in this family. Muscle biopsy samples of advanced cases showed ragged-red fibers, focal cytochrome c oxidase deficiency, and multiple mtDNA deletions by Southern blot analysis. An autosomal dominant mode of inheritance was evident with anticipation in successive generations. Linkage analysis excluded the chromosome 10q23.3-q24.3 region reported as being linked to the disease in a Finnish family with autosomal dominant progressive external ophthalmoplegia. We report for the first time clinical evidence for anticipation in a family with autosomal dominant progressive external ophthalmoplegia. We hypothesize that the nuclear gene causing this enigmatic disorder may be directly influenced by an expansion of an unstable DNA sequence and that the resulting phenotype is caused by a concerted action with multiple deletions of mtDNA.read more
Citations
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Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study.
Petri Luoma,Atle Melberg,Juha O. Rinne,Jyrki Kaukonen,Nina N. Nupponen,Richard M Chalmers,Anders Oldfors,Ilkka Rautakorpi,Leena Peltonen,Kari Majamaa,Hannu Somer,Anu Suomalainen +11 more
TL;DR: Cosegregation of parkinsonism and POLG mutations in seven families suggests that when defective, this gene can underlie mendelian transmission of Parkinsonism.
Journal ArticleDOI
Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients
Ann Gardner,Anna L.V. Johansson,Rolf Wibom,Inger Nennesmo,Ulrika von Döbeln,Lars Hagenfeldt,Tore Hällström +6 more
TL;DR: Investigating mitochondrial function in selected depressed patients in search of an aetiological or pathophysiological factor common to both depression and physical symptoms suggested that mitochondrial dysfunction is associated with vulnerability to psychopathology in this selected patient group.
Journal ArticleDOI
Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia.
G. Van Goethem,J.J. Martin,Bart Dermaut,Ann Löfgren,A Wibail,D. Ververken,P. Tack,I. Dehaene,M. Van Zandijcke,M Moonen,Chantal Ceuterick,P. De Jonghe,C. Van Broeckhoven +12 more
TL;DR: The first finding of a genetic cause of Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoparesis is reported and it implies that this disorder may actually be a variant of autosomal recessive progressive external ophthalmoplegia.
Journal ArticleDOI
Dominant inheritance of premature ovarian failure associated with mutant mitochondrial DNA polymerase gamma
Alistair T. Pagnamenta,Jan-Willem Taanman,Callum Wilson,Neil E Anderson,Rosetta Marotta,Andrew J. Duncan,Maria Bitner-Glindzicz,Robert W. Taylor,Adrienne Laskowski,David R. Thorburn,Shamima Rahman +10 more
TL;DR: This study confirms that POLG mutations can segregate with POF and parkinsonism and demonstrates for the first time that the Y955C mutation can lead to mtDNA depletion.
Journal ArticleDOI
Structural and functional brain asymmetries in human situs inversus totalis
David N. Kennedy,K. M. O'Craven,Baruch S. Ticho,Allan M. Goldstein,Nikos Makris,John W. Henson +5 more
TL;DR: The developmental factors determining anatomic asymmetry of the cerebral petalia and viscera are distinct from those producing the functional lateralization of language, suggesting that the human brain is asymmetric in structure and function.
References
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