2008 Woodie Awards
Two rare diseases share overlapping genetics
Issue date: 3/13/08
As scientists start to discover the genetic basis for human health and behavior, they have come across some surprising findings. For example, even a single gene can cause multiple diseases, depending on how it is altered or mutated.
Sometimes diseases once thought to be distinct because of their symptoms turn out to be biochemically quite similar.
Hopkins researchers have uncovered an example of this with the identification of two sets of genetic alterations, or mutations, that cause two distinct illnesses from the same genes.
One of the diseases is Meckel-Gruber Syndreme, also known as MKS. MKS is a severe disorder of fetal development that is almost always fatal in newborn babies. Although the disease is rare, it is related to more common disorders including cleft palate and brain malformations.
Scientists have identified mutations in at least three genes that cause MKS. The Hopkins group studied the genetic sequences of MKS1, MKS3, and CEP290. Surprisingly, the researchers found that changes in all three genes can cause an entirely different disorder, Bartlet-Biedl Syndrome, or BBS.
BBS is characterized by obesity, the presence of extra fingers and toes, or polydactyly, and mental retardation.
The scientists have put forward the hypothesis that, although these two diseases have different clinical presentations, from the perspective of a geneticist they might not be that distinct.
In studies in mice and zebrafish, the researchers showed that changes in the genes can cause both disorders. Mice with BBS-linked mutations also showed defects in the neural tube, the precursor to the brain and spinal cord that is commonly affected in MKS.
Overall, they found that mutations in all three BBS genes cause MKS-like effects.
The researchers argue that MKS might just be a severe variant of BBS, even though their manifestations are different. This finding was only possible through the lens of genetics.
To further evaluate their hypothesis, the scientists studied the genes of families with BBS or MKS. Most of the families showed genetic similarities on a molecular level.
Despite the continued ambiguity in this area, the genetic findings have contributed valuable information by linking these rare disorders to each other and to more common diseases about which more is known.
Sometimes diseases once thought to be distinct because of their symptoms turn out to be biochemically quite similar.
Hopkins researchers have uncovered an example of this with the identification of two sets of genetic alterations, or mutations, that cause two distinct illnesses from the same genes.
One of the diseases is Meckel-Gruber Syndreme, also known as MKS. MKS is a severe disorder of fetal development that is almost always fatal in newborn babies. Although the disease is rare, it is related to more common disorders including cleft palate and brain malformations.
Scientists have identified mutations in at least three genes that cause MKS. The Hopkins group studied the genetic sequences of MKS1, MKS3, and CEP290. Surprisingly, the researchers found that changes in all three genes can cause an entirely different disorder, Bartlet-Biedl Syndrome, or BBS.
BBS is characterized by obesity, the presence of extra fingers and toes, or polydactyly, and mental retardation.
The scientists have put forward the hypothesis that, although these two diseases have different clinical presentations, from the perspective of a geneticist they might not be that distinct.
In studies in mice and zebrafish, the researchers showed that changes in the genes can cause both disorders. Mice with BBS-linked mutations also showed defects in the neural tube, the precursor to the brain and spinal cord that is commonly affected in MKS.
Overall, they found that mutations in all three BBS genes cause MKS-like effects.
The researchers argue that MKS might just be a severe variant of BBS, even though their manifestations are different. This finding was only possible through the lens of genetics.
To further evaluate their hypothesis, the scientists studied the genes of families with BBS or MKS. Most of the families showed genetic similarities on a molecular level.
Despite the continued ambiguity in this area, the genetic findings have contributed valuable information by linking these rare disorders to each other and to more common diseases about which more is known.
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