What is French Settlement Disease?
French Settlement Disease (FSD) is a rare, inherited disease
named after the small community where it was first discovered. French
Settlement, Louisiana, is located on the Amite River, about 90 miles northwest
of New Orleans. The town of about 1000 is part of Livingston Parish, which is
the Louisiana equivalent of a county.
For generations, residents of French Settlement have been
aware of a rare genetic disease. It was first reported in the medical
literature in 1979. FSD is inherited in an autosomal recessive fashion which
means that the affected child must inherit the gene from both parents. FSD
belongs to the group of genetic diseases called Hereditary Spastic Paraplegias.
The underlying genetic cause of FSD is not yet known.
https://www.medschool.lsuhsc.edu/genetics_center/louisiana/article_french.htm
Similarly, a long-term program is the prospect for
developing a means to control the condition we have named French Settlement Disease
(FSD). That disease is unique to the descendants of settlers in Livingston Parish
of Louisiana.
The disease is
one of a group of disorders known collectively by the
medical name, hereditary spastic paraplegia. Understand each word of that
phrase -- hereditary spastic paraplegia -- and you will
understand the basic
concept of this disease.
1. Hereditary - received from parents of
ancestors
2. Spastic - muscles are stiff and the movements
awkward
3. Paraplegia - slight or incomplete paralysis
of the lower part of the body
FSD, therefore, is an inherited defect in which certain
chemical reactions
in the body do not proceed normally, resulting in serious
disturbances in
the function of the specialized nerves that control not only
body movement
but also speech and other processes.
In the past few
years, we have focused our efforts on FSD and several
similar diseases.
Strides have already been made in accumulating the know-
ledge needed to control FSD.
But no cure is available yet, and one is not
likely soon. This
leaflet gives an up-to-date report on current progress
and hopes for the future.
What causes the disease?
Until recently
that question would have been difficult to answer. However, we now have evidence that FSD occurs when a
specific chemical )an enzyme) is missing in the body. An enzyme is a protein that aids in the body's chemical processes.
Some enzymes convert starch into sugar.
Others help the body get rid of excess sugar. Still others are necessary for the normal production and utilization of fats (sometimes
called lipids.) Literally thousands of different enzymes are necessary for
life. Although the search for the specific FSD-related enzyme
continues, that
enzyme has not yet been identified.
French Settlement, Louisiana, is an unassuming little town
just northwest of New Orleans. It is also the place where a group of genetic
disorders known as hereditary spastic paraplegia (HSP), or French Settlement
Disease, was first discovered. Unlike the town, the disease is anything but
modest: its main features are stiffness and involuntary contractions in the
legs. Thirty-five years after the disease’s discovery, a study led by HHMI
Investigator Joseph Gleeson at the University of California, San Diego, has
almost doubled the number of genes associated with HSP.
Scientists had already linked 22 genes to HSP, but mutations
in those genes explained less than 50 percent of the cases. To find more genes,
Gleeson and a team of 51 scientists from around the world recruited 55 families
with HSP. The scientists sequenced every gene in 93 family members and
discovered 18 genes newly linked to the disease. They then created an
“HSPome”—a genetic map showing how all the HSP-associated genes interact with
each other.
The effort, which took 10 years, allowed the researchers to
link HSP to other common neurodegenerative diseases, such as Alzheimer’s. “This
told us that common neurodegenerative diseases share similar networks and
cellular vulnerabilities,” says Gleeson. “Maybe we need to think about these
less as individual diseases and more as collective problems of neuronal
susceptibility.”
The findings, reported January 31, 2014, in Science, may
help Gleeson and his colleagues develop new treatments for HSP. They’re already
pursuing several promising targets.
https://www.hhmi.org/bulletin/spring-2014/roots-disease
Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL,
Heiberg AD, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A,
Kayserili H, Al-Aama JY, Abdel-Salam GMH, Karminejad A, Kara M, Kara B, Bozorgmehri
B, Ben-Omran T, Mojahedi F, El Din Mahmoud IG, Bouslam N, Bouhouche A,
Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N,
Al-Allawi N, Bindu PS, Azam M, Gunel M, Caglayan A, Bilguvar K, Tolun A, Issa MY,
Schroth J, Spencer EG, Rosti RO, Akizu N, Vaux KK, Johansen A, Koh AA, Megahed H,
Durr A, Brice A,
Stevanin G, Gabriel SB, Ideker T, Gleeson JG. Exome
sequencing links corticospinal motor neuron disease to common
neurodegenerative disorders. Science. 2014 Jan 31;343(6170):506-511.
Abstract
Hereditary spastic paraplegias (HSPs) are neurodegenerative
motor neuron diseases characterized by progressive age-dependent loss of
corticospinal motor tract function. Although the genetic basis is partly
understood, only a fraction of cases can receive a genetic diagnosis, and a
global view of HSP is lacking. By using whole-exome sequencing in combination
with network analysis, we identified 18 previously unknown putative HSP genes
and validated nearly all of these genes functionally or genetically. The
pathways highlighted by these mutations link HSP to cellular transport,
nucleotide metabolism, and synapse and axon development. Network analysis
revealed a host of further candidate genes, of which three were mutated in our
cohort. Our analysis links HSP to other neurodegenerative disorders and can
facilitate gene discovery and mechanistic understanding of disease.
No comments:
Post a Comment