Next Generation Sequencing Mitochondrial DNA Analysis in Autism Spectrum Disorder.
Ashok Patowary, Ryan Nesbitt, Marilyn Archer and 2 others
PMID 28419775WHAT IT FOUND
Rare mitochondrial DNA variants were shared by affected members of ten autism families, including two variants previously seen in mitochondrial disease.
This cannot show these variants cause autism or change therapy.
Key findings
01The study sequenced 35 individuals in families with autism and found 5 rare mitochondrial DNA variants that met its criteria for interest.
02Two rare MT-ND5 mitochondrial variants were identified in one family, and they had been reported in other families with mitochondrial eye or multisystem disease.
03In a cousin family, one rare MT-ATP6 mitochondrial variant and one novel NDUFS4 nuclear variant were found, but computer predictions did not agree and no published lab studies of variant effects were available.
STILL TO COME
How it was doneWhat they foundWhat it means for SLPs
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What it does not show
The sample was small and selected: ten families and 35 individuals chosen for extended maternal lineage or multiple affected siblings, and the authors say further analyses in adequately powered samples are needed. The authors lacked detailed clinical information on affected subjects and genotype information for parents and unaffected relatives, so they could not assess mitochondrial disease features or whether variants led to disease in carriers. Samples came from lymphoblastoid cell lines, not brain tissue, and the authors note a difference in mutation profile might be present. For the MT-ND5 variants, computer predictions were not uniformly consistent with a harmful role, although other studies reported functional effects. For the MT-ATP6 and NDUFS4 variants, computer predictions did not agree and no published lab studies of variant effects were available. The authors say more detailed clinical information about affected people is needed.
The easy way to misread this
Do not read the identification of rare mitochondrial variants as evidence that mitochondrial dysfunction causes autism or that genetic testing should guide therapy. The families were selected for likely mitochondrial inheritance, the paper could not assess clinical mitochondrial disease features or whether variants led to disease in carriers, and the authors say larger and more detailed studies are needed.