Gene Mutation Associated With Degenerative Disease of Brain Blood Vessels Identified

A rare genetic disorder called leukoencephalopathy with cerebral calcifications and cysts is linked to a mutation in SNORD118.

Highlights

Scientists carry out 12-year research on the cause for leukoencephalopathy with cerebral calcifications and cysts (LCC).
SNORD118 gene mutation found to be associated with LCC.
Identification of the gene could improve diagnosis and treatment for the condition.

A single gene mutation has been found to be associated with leukoencephalopathy - a degenerative and debilitating disease which involves the blood vessels of the brain.

Dr. Yanick Crow and Dr. Ray O'Keefe from the Department of Evolution and Genomic Sciences at The University of Manchester, carried out this experiment for over 12 years with inputs from more than 60 scientists and academicians. The cause of this disease has long been unknown and it is a very rare disease. The current study provides an insight into the possible cause of the disease.

Genetic Testing Procedure
In most cases genetic testing is done using blood samples. Other tissues and body fluids like skin, hair, bone marrow, amniotic fluid and semen are also employed

‘Identifying mutations associated with non-coding RNA aids in better understanding of diseases caused by non-protein coding part of the genome.’

A Case of Leukoencephalopathy, Cerebral Calcifications and Cysts

Ajay Gulati and colleagues describe a 36-year-old patient who presented with the triad of leukoencephalopathy along with cerebral calcifications and cysts in their paper titled “A case of leukoencephalopathy, cerebral calcifications and cysts”.

The patient was found to have

Simple partial seizures
Weakness of the right upper limb
Tremor
Mild right lower limb weakness
There was reduced muscle power on neurological examination of the right side
Mild spasticity
There was extensive calcification in the basal ganglia, bilateral deep cerebral nuclei and the right thalamus.
Cystic lesions that were large and round were found in the occipitotemporal region.

When a serological test was performed to identify the source of this disease, there was no source of infection.

Tale on Genome Sequencing Diagnostics for Congenital Disorders of Glycosylation
Children who are born with rare, inherited conditions known as Congenital Disorders of Glycosylation or CDG, have mutations in one of the many enzymes the body uses to decorate its proteins and cells with sugars.

Single Gene Mutation - SNORD118

The researchers Dr. Yanick Crow and colleagues, after studying the disease for a period of 12 years, have been able to identify a single gene mutation that could lead to the development of this disease. The mutation at SNORD118 found using gene sequencing was associated with leukoencephalopathy along with cerebral calcifications and cysts.

Next Generation Gene Sequencing in Newborns May Improve Disease Diagnosis
Newborns admitted to the NICU with rare and complex diseases may benefit substantially from a timely molecular diagnosis through next-generation sequencing.

Research associate, Dr. Emma Jenkinson from the Department of Evolution and Genomic Sciences at The University of Manchester says “The identification of SNORD118 as the instigator of a progressive and frequently fatal brain disease is a very significant step forward in understanding the role of non-coding RNAs in the development of certain diseases.”

Non-Coding RNAs

Microrna Silencing Provides a New Model for Cancer Treatment
Since the discovery that microRNAs play key roles in regulating human disease, the hope has been that these RNA molecules could be translated into a therapeutic strategy for cancer treatment.

Non-coding RNAs have been extensively studied in the various cancers of the body due to the expression and function of a large number of micro RNAs in cancer. There have been numerous studies that have been undertaken to identify the significance of these genes and their role in disease development and progression.

The studies have found an association between a dysregulation of these non-coding regions of RNA and tumorigenesis along with association with certain developmental, neurological and cardiovascular disease.

Identifying the Gene

33 families that were affected by leukoencephalopathy with cerebral calcifications and cysts (LCC) were identified and biological samples from them were collected. The mutated gene was identified using the next generation of genome sequencing technique.

Dr. Emma talks about the merit of identifying the gene “Although LCC is relatively rare, by understanding the mechanism of this disease we may be able to extrapolate similar research into other diseases in the future - with the ultimate long term aim being the discovery of new treatments for patients."

Gene sequencing of the biological samples from the 33 families provided the scientists with 33 gene variants and when these variants were studied, many of them were found to cause the disease.

LCC is a rare disease but identifying this gene will aid in early detection of the disease with preventive strategies initiated to control the white brain degeneration that could occur. The disease which can develop at any stage of life can be debilitating and result in premature death.

References:

A case of leukoencephalopathy, cerebral calcifications and cysts - (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3271476/)
Non-coding RNAs in human disease - (http://www.ncbi.nlm.nih.gov/pubmed/22094949)

Source-Medindia