Research team in CSIR-IGIB led by Dr. Sridhar Sivasubbu and Dr. Vinod Scaria along with Clinical collaborators from the Government Medical College Kozhikode in Kerala has successfully diagnosed an inconclusive case of Neuronal ceroid-lipofuscinosis (NCL) using Whole Exome sequencing
Aswini B | 05 September 2019
Neuronal ceroid-lipofuscinosis (NCL) is a rare genetic disorder. More than 300 cases have been reported in scientific literature from around the world. Accumulation of ceroid (pigmented lipid derived from fat droplets) and lipofuscin (pigmented lipid resulting from degradation of membranes) are found in the cytoplasm of the cells in these patients as a result of defective lysosomal storage. This results in the destruction of neuronal cells leading to various neuro-degenerative phenotypes like brain atrophy and loss of vision.
Multiple genes are found to be involved in NCL and more than 446 mutations in these genes are reported in the NCL mutation database (ucl.ac.uk/ncl/mutation). This complexity has made diagnosis difficult.
Research group in CSIR IGIB led by Dr. Sivasubbu and Dr. Scaria along with clinical collaborators at the Government Medical College, Kozhikode have have identified the involvement of a homozygous mutation in the Cathepsin D (CTSD) gene using exome sequencing, in a rare inconclusive case of NCL type 10. The mutation, changes a particular amino acid in the gene which is crucial for its activity. Using sanger sequencing they found heterozygous mutation of the same gene in the parents.
Since, lipofuscin deposits can be observed in other tissues of the body as well, they have evaluated skin biopsies using transmission electron microscopy (TEM) and found small membrane-bound cavities of different sizes in the cells, similar to lipofuscin deposits, in all layers of skin. With the genotype–phenotype correlation, they have confirmed the diagnosis of NCL type 10.
From this study, they have demonstrated that genetic testing using whole exome sequencing aids in accurate and timely diagnosis of a rare neurodegenerative disorder, NCL10.
This work was published in Neurology Genetics on April 2019. The article is available online at https://doi.org/10.1212/NXG.0000000000000302
Aswini B | 05 September 2019
Neuronal ceroid-lipofuscinosis (NCL) is a rare genetic disorder. More than 300 cases have been reported in scientific literature from around the world. Accumulation of ceroid (pigmented lipid derived from fat droplets) and lipofuscin (pigmented lipid resulting from degradation of membranes) are found in the cytoplasm of the cells in these patients as a result of defective lysosomal storage. This results in the destruction of neuronal cells leading to various neuro-degenerative phenotypes like brain atrophy and loss of vision.
Multiple genes are found to be involved in NCL and more than 446 mutations in these genes are reported in the NCL mutation database (ucl.ac.uk/ncl/mutation). This complexity has made diagnosis difficult.
Research group in CSIR IGIB led by Dr. Sivasubbu and Dr. Scaria along with clinical collaborators at the Government Medical College, Kozhikode have have identified the involvement of a homozygous mutation in the Cathepsin D (CTSD) gene using exome sequencing, in a rare inconclusive case of NCL type 10. The mutation, changes a particular amino acid in the gene which is crucial for its activity. Using sanger sequencing they found heterozygous mutation of the same gene in the parents.
Since, lipofuscin deposits can be observed in other tissues of the body as well, they have evaluated skin biopsies using transmission electron microscopy (TEM) and found small membrane-bound cavities of different sizes in the cells, similar to lipofuscin deposits, in all layers of skin. With the genotype–phenotype correlation, they have confirmed the diagnosis of NCL type 10.
From this study, they have demonstrated that genetic testing using whole exome sequencing aids in accurate and timely diagnosis of a rare neurodegenerative disorder, NCL10.
This work was published in Neurology Genetics on April 2019. The article is available online at https://doi.org/10.1212/NXG.0000000000000302