Isolated distal myopathy of the upper limbs associated with mitochondrial DNA depletion and polymerase gamma mutations.
OBJECTIVE
To describe an unusual clinical phenotype in an adult harboring 2 compound heterozygous polymerase γ (POLG) mutations.


METHODS
Case report.


METHODS
University-based outpatient neurology clinic and pathology and genetics laboratory.


METHODS
A 27-year-old man presenting with isolated distal myopathy of the upper extremities in the absence of sensory disturbances.


RESULTS
Histochemical analysis of a muscle biopsy specimen showed numerous cytochrome c oxidase-deficient fibers. Molecular analysis revealed marked depletion of muscle mitochondrial DNA in the absence of multiple mitochondrial DNA deletions. Sequence analysis of the POLG gene revealed heterozygous sequence variants in compound c.1156C>T (p.R386C) and c.2794C>T (p.H932Y) segregating with clinical disease in the family. The p.R386C change appears to be a novel mutation.


CONCLUSIONS
Our case broadens the phenotypic spectrum of disorders associated with POLG mutations and highlights the complex relationship between genotype and phenotype in POLG-related disease.
Giordano
Carla
C
Department of Experimental Pathology, Sapienza University, Policlinico Umberto I, Roma, Italy.
Pichiorri
Floriana
F
Blakely
Emma L
EL
Perli
Elena
E
Orlandi
Maurizia
M
Gallo
Pietro
P
Taylor
Robert W
RW
Inghilleri
Maurizio
M
d'Amati
Giulia
G
D000328:Adult; D001132:Arm; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D049310:Distal Myopathies / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*
D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human