Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children.
OBJECTIVE
We studied the prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children in a defined population in Northern Ostrobothnia, Finland.


METHODS
Children with diagnoses commonly associated with mitochondrial diseases were ascertained. Blood DNA from 522 selected children was analyzed for 3243A>G. Children with the mutation were clinically examined. Information on health history before the age of 18 years was collected from previously identified adult patients with 3243A>G. Mutation segregation analysis in buccal epithelial cells was performed in mothers with 3243A>G and their children whose samples were analyzed anonymously.


RESULTS
Eighteen children were found to harbor 3243A>G in a population of 97,609. A minimum estimate for the prevalence of 3243A>G was 18.4 in 100,000 (95% confidence interval, 10.9-29.1/100,000). Information on health in childhood was obtained from 37 adult patients with 3243A>G. The first clinical manifestations appearing in childhood were sensorineural hearing impairment, short stature or delayed maturation, migraine, learning difficulties, and exercise intolerance. Mutation analysis from 13 mothers with 3243A>G and their 41 children gave a segregation rate of 0.80. The mothers with heteroplasmy greater than 50% tended to have offspring with lower or equal heteroplasmy, whereas the opposite was true for mothers with heteroplasmy less than or equal to 50% (p = 0.0016).


CONCLUSIONS
The prevalence of 3243A>G is relatively high in the pediatric population, but the morbidity in children is relatively low. The random genetic drift model may be inappropriate for the transmission of the 3243A>G mutation.
Uusimaa
Johanna
J
Department of Paediatrics, University of Oulu, Oulu, Finland.
Moilanen
Jukka S
JS
Vainionpää
Leena
L
Tapanainen
Päivi
P
Lindholm
Päivi
P
Nuutinen
Matti
M
Löppönen
Tuija
T
Mäki-Torkko
Elina
E
Rantala
Heikki
H
Majamaa
Kari
K
D000328:Adult; D001827:Body Height / Q000235:genetics; D002648:Child; D020090:Chromosome Segregation / Q000235:genetics; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics*; D004847:Epithelial Cells; D017079:Exercise Tolerance / Q000235:genetics; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D040961:Genetic Drift; D006128:Growth / Q000235:genetics / Q000502:physiology; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics; D017241:MELAS Syndrome / Q000235:genetics; D008297:Male; D008881:Migraine Disorders / Q000235:genetics; D028361:Mitochondrial Diseases / Q000235:genetics*; D009061:Mouth Mucosa / Q000166:cytology; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D010641:Phenotype