Gene change makes same disorder look different

March 10th, 2008 - 11:34 am ICT by admin  

New York, March 10 (IANS) Alterations in one’s genome might make a range of symptoms seem like entirely different disorders, a new study has found. The discovery by Johns Hopkins researchers that two clinically different inherited syndromes are actually variations of the same disorder could have far-reaching implications for treatment.

“Clinicians can finally begin to offer more accurate diagnoses based on the state of affairs at the cellular / biochemical level,” said Nicholas Katsanis of Hopkins, because “they share the same molecular underpinning”.

Findings of the study have been published in the latest issue of the journal Nature Genetics.

Katsanis’s team studies Bardet-Biedl syndrome (BBS) characterised by a combination of vision loss, obesity, diabetes, extra digits and mental defects and caused by faulty cilia - tiny hair like projections found on the body’s cells.

Recently they started examining Meckel-Gruber syndrome (MKS), which also shows cilia dysfunction but is clinically distinct from BBS and generally associated with prenatal or newborn death.

“While these two groups of patients exhibit such different clinical outcomes, the genes associated with both syndromes all seemed to be pointing at the same culprit: cilia,” said Katsanis.

The researchers sequenced the MKS genes from 200 BBS patients and found six families that, in addition to carrying BBS genetic mutations, also carried mutations in MKS genes.

To figure out what, if any, effect these MKS mutations have on BBS, the team used a system they previously developed in zebra fish.

Knocking out BBS genes in zebra fish generates short fish with even shorter tails, among other malformations. Injecting normal BBS genes into these fish rescues them, resulting in normal looking fish.

The researchers reasoned that if MKS and BBS are indeed the same condition, then fish with the MKS genes knocked out should mimic the BBS knockout fish. They did.

The team then went on to test mutant versions of MKS genes in BBS fish and found that three genes originally attributed to MKS do indeed cause BBS or render the BBS defects more pronounced, increasing the number of BBS genes to 14 in total.

“From a clinical perspective, these two syndromes look nothing alike, but… Meckel-Gruber and Bardet-Biedel actually represent a continuum of one disease. This never would have been discovered in the clinic - only molecular analysis can reveal these things.”

Katsanis hoped that the growing body of molecular data would help move medicine away from symptom-defined syndromes, which can leave clinicians struggling with ambiguous diagnoses.

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