Coexistence of mitochondrial and nuclear DNA mutations in a woman with mitochondrial encephalomyopathy and double cortex.
We describe a 16-year-old girl with mental retardation, myoclonic epilepsy, ataxia, mitochondrial myopathy, sensorineural hearing loss, lactic acidosis, and MRI evidence of diffuse subcortical laminar heterotopia and agyria/pachygyria. Restriction fragment length polymorphism (RFLP) and DNA sequence analyses revealed two pathogenic mutations: a heteroplasmic m.3243A>G in muscle and blood, and a new heterozygous insertion at nt697 in the doublecortin gene (DCX), resulting in a frameshift after amino acid residue 232, with a premature stop codon at amino acid residue 244. This is yet another example of genetic "double trouble" resulting in a complex phenotype.
Scuderi
Carmela
C
Unità Operativa di Malattie Neuromuscolari, IRCCS Oasi Maria SS, Troina, Italy. cscuderi@oasi.en.it
Borgione
Eugenia
E
Castello
Filippa
F
Lo Giudice
Mariangela
M
Fichera
Marco
M
Elia
Maurizio
M
Amato
Carmelo
C
Savio
Maria
M
Di Blasi
Francesco Domenico
FD
Vitello
Girolamo Aurelio
GA
Romano
Salvatore
S
DiMauro
Salvatore
S
Musumeci
Sebastiano Antonino
SA
D000293:Adolescent; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000235:genetics*; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics*; D016172:DNA Fingerprinting; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009479:Neuropeptides / Q000235:genetics; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA
D018389:Codon, Nonsense; C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D004247:DNA