Image source: Dr. Bruce Chassey Laboratory. National Institute Of Dental Research. Li-shan. Photographer: Mike Mitchell

Inherited neuromuscular disease HSP

Genetic cause for hereditary spastic paraplegia identified

Scientists at St George’s, University of London, in collaboration with researchers from Germany, the USA, Tunisia and Iran have identified a new gene associated with the neuromuscular disorder, hereditary spastic paraplegia (HSP).

The study, published in Nature Communications, also highlights a potential mechanism for the disease, which is already being targeted in drug trials for Alzheimer’s and Huntington’s diseases.

HSP is an inherited condition that causes stiffness and weakness in the leg muscles, often leading to patients becoming wheelchair-bound. Gradually getting worse over time, and with no treatments currently available, patients can only be offered muscle relaxants, which help the muscles to cope with the inability to move smoothly. Some patients also go on to have problems with their eyes, and can have brain development issues too. Several genes have already been linked with the disorder, which causes degeneration of the nerves that lead down from the brain. But these genes only account for around two-thirds of patients with the condition. The new mutation, found in the gene RNF170 by the researchers, gives doctors the opportunity to test for the disease in the other third of patients with no clear genetic diagnosis.

If you have a child who starts walking fine, but slowly loses the ability to walk, perhaps eventually needing a wheelchair, that can be very difficult for the family and child to deal with

Yalda Jamshidi

The Genetics Research Centre at St George’s, is leading a programme to identify the genetic mutations causing diseases in undiagnosed patients. Families with varying issues, including muscle conditions, neurodevelopmental disorders and heart problems have all come through the Centre in the hope of receiving a diagnosis.

As with this study, the families coming to the Centre all have their genetic code sequenced and the researchers look for mutations in known genes that may have been missed during routine screening, and also mutations in genes not yet associated with disease. In this case, the scientists were able to identify and confirm the gene’s involvement in HSP with the help of GeneMatcher – a matchmaking site for genes and investigators. This tool helped to identify further families with RNF170 mutations from Germany, Tunisia and Iran. 

Once confirmed, the team then took the research a step further to try and understand the mechanism by which the gene causes HSP. As highlighted by Dr Daniel Osborn, a St George’s co-author, “despite their obvious differences, human and zebrafish neuromuscular development is very similar, making zebrafish a fantastic model to understand the mechanisms of HSP.”

portrait of Yalda Jamshidi
Dr Yalda Jamshidi
Source: St George's, University of London

“We switched off the gene in a zebrafish model of the disease,” says Dr Yalda Jamshidi, lead for the Genetics Research Centre at St George’s and one of the lead researchers on the study. “We found that this caused the fish to develop smaller eyes and heads, and have problems with movement. This fits with what we see in the patients.” Additional experiments in cells identified defects in the calcium signalling pathway essential for cell function. This pathway is already known to play a role in other diseases, such as Alzheimer’s and Huntington’s. The researchers hope that drugs being developed to tackle these diseases could also be used to improve treatments for HSP.

“Our ambition is to have a drug that will work for patients, as we don’t have any alternative treatments other than managing the condition,” adds Dr Jamshidi. “If you have a child who starts walking fine, but slowly loses the ability to walk, perhaps eventually needing a wheelchair, that can be very difficult for the family and child to deal with. We want to be able to test for the disease, and as soon as you know there’s a mutation, you can put them on a new drug and hopefully counteract the progressive decline.”


Source: St George's, University of London

21.10.2019

Read all latest stories

Related articles

Photo

CRISPR-Cas9

An 'on-off switch' for gene editing

Over the past decade, the CRISPR-Cas9 gene editing system has revolutionized genetic engineering, allowing scientists to make targeted changes to organisms’ DNA. While the system could potentially…

Photo

53,831 genomes analysed

Rare diseases: huge dataset brings new insights

Researchers at the University of Maryland School of Medicine (UMSOM) and their colleagues published a new analysis from genetic sequencing data of more than 53,000 individuals, primarily from…

Photo

Coronavirus genome folding

Researchers prepare for “SARS-CoV-3”

For the first time, an international research alliance has observed the RNA folding structures of the SARS-CoV2 genome with which the virus controls the infection process. This could not only lay the…

Related products

Orion Diagnostica Oy – Orion GenRead

Amplification

Orion Diagnostica Oy – Orion GenRead

Orion Diagnostics Oy
Sarstedt – Low DNA Binding Micro Tubes

Research Use Only (RUO)

Sarstedt – Low DNA Binding Micro Tubes

SARSTEDT AG & CO. KG
Sarstedt – White Multiply PCR Plates

Amplification

Sarstedt – White Multiply PCR Plates

SARSTEDT AG & CO. KG
Gene Science – Saliva Collection Kit

Gene Science – Saliva Collection Kit

Zhejiang Gene Science Co., Ltd.
Genrui – NE48

Extraction

Genrui – NE48

Genrui Biotech Inc.
Subscribe to Newsletter