Rare window on spinal muscular atrophy genetics

Apr 07, 2009

Caused by a mutation of the SMN gene, spinal muscular atrophy (SMA) is an infantile and juvenile neurodegenerative disorder where motor neuron loss causes progressive paralysis. A new study published in the open access journal BMC Medicine details the first research focused on human muscle tissue atrophied due to a genetic condition, and sheds light on two distinct mechanisms at work in different forms of SMA.

A research team from Italy, led by Gerolamo Lanfranchi, analyzed muscle biopsies and genomic DNA from peripheral blood of four SMA I and five SMA III patients from the Neuromuscular Bank organised by Corrado Angelini at the University of Padova, to investigate which other muscle genes, other than the SMN defect, played a role in atrophy. They used microarray and quantitative real-time PCR to study at transcriptional level the effects of a defective SMN gene in skeletal muscles affected by the two forms of SMA: the most severe, type I (infantile), and the milder type III (juvenile).

SMA type I is also known as severe infantile SMA or Werdnig-Hoffmann disease. Manifesting rapidly in infants, babies diagnosed with type I SMA do not generally live past one year of age. SMA type III represents a milder form of the disorder. It has a later onset and affected patients may be able to walk but later lose this ability.

The two forms of SMA gave distinct expression signatures. The SMA III muscle transcriptome is close to normal, whereas in SMA I is significantly altered. Genes implicated in signal transduction were up-regulated in SMA III whereas those involved in energy metabolism and muscle contraction were consistently down-regulated in SMA I.

"Our work indicates that SMA I and III muscles are in different phases: the 'prolonged' atrophic condition typical of the SMA I muscle and the coexistence of atrophy and hypertrophy in SMA III muscle," says Lanfranchi.

Previous studies have investigated transcriptional changes in mouse or rat muscle atrophied due to physiopathological conditions, but this is the first to use human tissue affected by a genetic atrophic condition.

More information: ifferent atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy , Caterina Millino, Marina Fanin, Andrea Vettori, Paolo Laveder, Maria Luisa Mostacciuolo, Corrado Angelini and Gerolamo Lanfranchi, BMC Medicine (in press), www.biomedcentral.com/bmcmed/

Source: BioMed Central (news : web)

Explore further: Mouse study reveals potential clue to extra fingers or toes

add to favorites email to friend print save as pdf

Related Stories

Toward an effective treatment for a major hereditary disease

Oct 13, 2008

Scientists are reporting a key advance toward developing the first effective drug treatment for spinal muscular atrophy (SMA), a genetic disease that involves motor neuron loss and occurs in 1 out of every 6,000 births. SMA ...

Researchers gain new insights on spinal muscular atrophy

May 29, 2008

Researchers from the University of Pennsylvania School of Medicine discovered that the effect of a protein deficiency, which is the basis of the neuromuscular disease spinal muscular atrophy (SMA), is not restricted to motor ...

Patient-derived induced stem cells retain disease traits

Dec 21, 2008

(PhysOrg.com) -- When neurons started dying in Clive Svendsen's lab dishes, he couldn't have been more pleased.The dying cells – the same type lost in patients with the devastating neurological disease spinal ...

Recommended for you

Stress reaction may be in your dad's DNA, study finds

38 minutes ago

Stress in this generation could mean resilience in the next, a new study suggests. Male mice subjected to unpredictable stressors produced offspring that showed more flexible coping strategies when under ...

More genetic clues found in a severe food allergy

2 hours ago

Scientists have identified four new genes associated with the severe food allergy eosinophilic esophagitis (EoE). Because the genes appear to have roles in other allergic diseases and in inflammation, the ...

Brain-dwelling worm in UK man's head sequenced

19 hours ago

For the first time, the genome of a rarely seen tapeworm has been sequenced. The genetic information of this invasive parasite, which lived for four years in a UK resident's brain, offers new opportunities ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.