Biology of CLN7

How CLN7 Disease Affects the Body

CLN7 disease affects children both cognitively and physically. Symptoms of the disease may include:

Science Behind CLN7 Disease

The underlying cause of CLN7 disease is found in an individual’s genetic code. In humans, each cell contains 23 pairs of chromosomes for a total of 46: 23 from their mother and 23 from their father. The first 22 pairs of chromosomes are autosomesAny chromosome in a cell that is not an X or Y sex chromosome. The average person has 22 pairs of autosomes (44 autosomes in total) in each cell that define the genetic make-up, or DNA, of the being. These chromosomes store thousands of genes and they are inherited from the beings’ parents. In addition to the 22 pairs of autosomes (44 total), beings also have one pair (2 total) sex chromosomes (X and Y in a male, and X and X in a female)., and they look the same in both males and females. The 23^rd pair are sex chromosomes, which are different between males and females. Females have two copies of the X chromosomes (XX) and males have one X and one Y chromosome (XY). A variantA variant is a change in DNA. A variant may or may not cause disease. The following modifiers describe the variant: (i) pathogenic, (ii) likely pathogenic, (iii) uncertain significance, (iv) likely benign, or (v) benign depending on whether or not the variant causes disease. For example, a “pathogenic variant” may cause disease. The term “variant” has replaced the term “mutation.” in a gene on one of the first 22 autosomes can lead to an autosomalInheritance characteristic where a gene is located on a numbered, non-sex chromosome. These are found on one of the 22 pairs of (44 total) autosomal chromosomes in a human body where DNA is stored. This is one of several ways that a trait, disorder, or disease can be passed down through families. These chromosomes are not the sex (X or Y) chromosomes. disease.

Autosomal recessive is one of several ways that a disorder or disease is passed down through families. An autosomal recessive disorder occurs when a child inherits two copies of a mutated gene, one from the mother and one from the father. The biological parents, known as carriers, each carry only one copy of the mutated gene, and usually do not show symptoms of the disease.

CLN7 disease is inherited in an autosomal recessive pattern, meaning both copies of the CLN7 gene variant (one from each parent, or carrier) must be present for the child to be diagnosed with CLN7 disease.

Healthy CLN7 Gene

A healthy CLN7 gene provides the body with instructions for building the CLN7 protein. Although the exact function of the protein is unknown, it is thought to transport molecules across the lysosomal membrane — resulting in normal cellular function.

CLN7 Variant

People with CLN7 disease have a variant on the CLN7 gene, also known as the MFSD8 gene, located on chromosome 4. When there is a variant or mutationA mutation is any inherited genetic change. The term “mutation” is being replaced by the term “variant.” in the CLN7 gene, the body creates a non-functional CLN7 protein that cannot transport molecules across the lysosomal membrane, resulting in lysosomal dysfunction. The lysosomeSpecialized vesicles within cells that digest large molecules, breaking down excess waste products of the cell with the help of enzymes. Lysosomes may also be used to destroy invading viruses and bacteria., when unable to function properly, causes an accumulation of molecules throughout the body and causes cell death.

Although the CLN7 protein is expressed throughout the body, nerve cells seem to be the most impacted, leading to the central nervous system-related signs and symptoms seen in patients who have CLN7.

Sources:

1. Sharifi, A., Kousi, M., Sagné, C., Bellenchi, G. C., Morel, L., Darmon, M., Hůlková, H., Ruivo, R., Debacker, C., El Mestikawy, S., Elleder, M., Lehesjoki, A. E., Jalanko, A., Gasnier, B., & Kyttälä, A. (2010, Nov.). Expression and lysosomal targeting of CLN7, a major facilitator superfamily transporter associated with variant late-infantile neuronal ceroid lipofuscinosis. Human Molecular Genetics, 19(22): 4497–4514. Retrieved December 17, 2019, from link.
2. Types of Batten DiseaseBatten disease is the common name for a broad class of rare, inherited disorders or diseases of the nervous system also known as neuronal ceroid lipofuscinoses, or NCLs. In these diseases, a defect in a specific gene triggers a cascade of problems that interferes with a cell’s ability to recycle certain molecules. The disease has several forms that share some of the same features and symptoms but vary in severity and age when symptoms first begin to appear. Each form is caused by a variant in a different gene. Although “Batten disease” originally referred specifically to the juvenile-onset form of NCL, the term Batten disease is increasingly used to describe all forms of NCL. The disease ultimately leads to shortened lifespan.. (n.d.). Retrieved August 14, 2019, from link.
3. CLN7 disease. (2019, July 16). Retrieved July 31, 2019, from link.
4. Neuronal ceroid lipofuscinosis 7. (n.d.). Retrieved July 31, 2019, from link.