New Possible SIDS Genes Identified

ScienceDaily is reporting that researchers at the Mayo Clinic have identified two more cardiac genes that could contribute to sudden infant death syndrome (SIDS). From the article: "In the two recent separate studies, researchers examined caveolin-3 (CAV3) and the cardiac ryanodine receptor (RyR2) and found molecular and functional evidence in both to implicate them as SIDS-susceptibility genes. Researchers examined the tissue of 135 unrelated cases of SIDS -- in infants with an average age of 3 months old -- that had been referred to Mayo Clinic's Sudden Death Genomics Laboratory for molecular autopsy. In each study, two of the 135 cases possessed mutations in either CAV3 or RyR2."

Comments

Seems an odd gene to still exist

[AuMatar]

Unless it has major advantages in youth/adult life. It increases the chance of death long before sexual maturity, evolution usually weeds those genes out rather quickly. Does the gene have any other known effect?

Re:Seems an odd gene to still exist

[Autumnmist]

RTFA.

The CAV3 and RYR2 genes are not the problems themselves. The problems come from specific MUTATIONS in those genes. The article specifically says: "In each study, two of the 135 cases possessed mutations in either CAV3 or RyR2."

And before anyone starts going "2/135 isn't much," the scientists didn't say these mutations alone are responsible for the disease. They say In the two recent separate studies, researchers examined caveolin-3 (CAV3) and the cardiac ryanodine receptor (RyR2) and found molecular and functional evidence in both to implicate them as SIDS-susceptibility genes. . Susceptibility is the key word here. Having the mutations doesn't guarantee SIDS; it only increases the likelihood of it.

Whenever you read a simplified article about genetic susceptibility, 9/10 times the "gene" that is linked to the disease doesn't actually mean the gene causes the disease. It means that mutations in the gene cause the disease.

The mutations impair the normal function of the gene. In the case of these two genes, CAV3 is the gene coding for a protein found in muscle and losing it results in muscle degeneration, while RYR2 is the gene coding for a calcium-release receptor in cardiac muscle.

Re:Seems an odd gene to still exist

[Bacon Bits]

Mutant powers in comic books:

• fast healing
• laser beam eyes
• teleportation
• control over weather

Mutant powers in real life:

• Early death (SIDS)
• Ability to grow useless diseased lumps of tissue (cancer)
• Impaired mental abilities (Down Syndrome)

This just doesn't seem fair.

Lots of work to do...

[MarkByers]

In each study, two of the 135 cases possessed mutations in either CAV3 or RyR2.

So one case of each mutation was found in each trial, and 266 of the 270 cases remain unsolved. It sounds like it is barely above a statistical anomaly.

If you take a random sample of 270 people that like fishing, there will be some mutation that is common between two or more of them, but that's hardly enough to claim that this mutation makes you enjoy fishing.

It looks like there is still a lot more research to do before we understand what the effects of different genes / mutations are.

Re:Lots of work to do...

[Idarubicin]

If you take a random sample of 270 people that like fishing, there will be some mutation that is common between two or more of them, but that's hardly enough to claim that this mutation makes you enjoy fishing.

You're assuming a 'fishing expedition' for any random gene mutation in common, though.

These studies looked specifically at genes that were known to be related to heart problems in adults. CAV3 was recently identified as a genetic cause of long QT syndrome, while RyR2 is linked to catecholaminergic polymorphic ventricular tachycardia (press release).

If these mutations occur at a low baseline rate in the general population, two hits of each may be quite significant. This link indicates that RyR2 mutations are rare in the general population, with a probable incidence of under 1%. (They found no mutations in 200 healthy volunteers having 400 copies of the gene.) I'm not going to dig further for incidence numbers, but I'd bet good money that both RyR2 and CAV3 mutations are rare and that getting two hits of each in a population of 135 is quite unlikely.

Good philosophy

[goldaryn]

Seems like a cool organisation. Wikipedia:
"Mayo Clinic is significant in the way the medical physicians' are paid. In most health care systems, medical doctors are paid based on the number of patients that they see. The more patients seen, the more a doctor gets paid. At Mayo Clinic, medical doctors are paid a salary that is unaffected by patient volume. This allows the doctors to spend time with their patients and not worry so much about time constraints. Physicians and surgeons have no undue influence upon them to do more procedures and operations."

That's a marvellous philosophy if you ask me, and they still made US$5.6 billion in 2004. Good for them.

Re:Color me skeptical, but...

[Idarubicin]

Something that occurs in less than 2% of studied cases is a "potential contributing cause"?

Yep. It's not that unusual, actually. Physicians and epidemiologists start out with a number of dead people. They look for commonalities: symptoms, age at onset, unusual blood chemistry, etc. If they don't know what the root cause of an ailment is but they see similar patterns across a number of deaths, they coin a name for it. Here, it's Sudden Infant Death Syndrome--SIDS.

The name tells you what happens but doesn't explain why. Saying "I have a runny nose and I've been sneezing a lot" would let me put you in the Sudden Adult Sniffling Syndrome (SASS) group, but it doesn't actually tell me what caused your ailment. It turns out that SASS actually has a number of different causes that ultimately lead to the same outcome. You may be having an allergic reaction to pollen. You might have a rhinovirus infection. Maybe you have a brain tumour. For this particular symptom, we have a lot of ways of evaluating the course of the disease and the status of the patient.

With SIDS it is much more difficult. There may be many factors that make an individual susceptible, some genetic, some environmental, some a combination, some requiring a lot of bad luck.

A comparison might be drawn with ALS (amyotrophic lateral sclerosis, known in the U.S. as Lou Gehrig's disease). In ALS, the motor neurons die off slowly, over the course of months or years. It starts in the periphery of the body and works its way up to the brain. Under the 'umbrella' of ALS, about 10% of cases are classified as 'familial'--that is, a patient is related to other individuals with the disease. Within this category, about 20% of cases are linked to one of several mutations in the gene SOD1 (superoxide dismutase). (One would expect most of the other familial cases to be related to other genes or gene combinations.) So while only about 2% of ALS cases are linked to SOD1 mutations, it is without a doubt a "contributing cause".