Abstract □ 114

A family who has lost a child to sudden infant death syndrome (SIDS) has a 6 times increased risk of loosing the next child. No mendelian trait has been shown. This fact, along with observations of increased sleepiness and a high level of hypoxanthine as sign of energy (ATP) deficiency, may indicate involvement of mtDNA mutations in SIDS, since mtDNA is inherited only from the mother.

A previous study from our institute showed that SIDS victims have a tendency towards a higher substitution rate in the hypervariable region of the displacement(D)-loop of mtDNA, than controls. The present study was set up to investigate whether all substitutions in the D-loop in SIDS can be recovered along the maternal line of the family (inherited substitutions), or whether SIDS victims have new substitutions compared to maternal relatives (somatic mutations) that could be related to environmental factors.

Material and method: Five SIDS families were studied. In one case bloodsamples were obtained from four generations. The D-loop sequences were recorded in the basepair range 16055-16500 in the mtDNA sequence. The sequencing was done using dye primer cycle sequencing and AmpliTaq polymerase FS on an ABI PRISM 377 DNA sequencer (Applied Biosystems, Perkin Elmer International Inc., Foster City, California, USA). The recorded D-loop sequences were compared with the Cambridge sequence, and differences were recorded as substitutions. The substitution pattern from the SIDS victim was then compared with the pattern found in the family members.

Results: In three families who have lost a child to SIDS, two or more substitutions in D-loop were found. These substitutions could all be traced in the maternal line of the family, in two cases two generations backwards, and in the case of a pair of homozygous twins, three generations backwards.

Discussion: In patients with known mtDNA disease a large number of sequence variants have been found in the D-loop region. Substitutions in the D-loop may be part of a haplotype with mutations elsewhere in the mtDNA. The study of D-loop substitutions in families with SIDS could indicate that a disposition to die from SIDS, in cases due to energy deficiency caused by mutations in mtDNA, is hereditary and not due to somatic mutations.

Conclusion: These preliminary results seem to indicate that substitutions in D-loop usually are recovered in the SIDS victims maternal relatives, and are thus not due to somatic mutations caused by environmental factors.