About time we moved on in the Chromosome Parade to chromosome 7. The disease gene I’d like to learn more about today is the dihydrolipoamide dehydrogenase (DLD) gene associated with maple syrup urine disease. The DLD gene creates a protein that is part of an enzyme complex which breaks down molecules in the mitochrondria.

Most DLD mutations change single amino acids in the E3 component, which alters the structure of the protein and prevents the BCKD enzyme complex from breaking down valine, isovaline, and leucine. As a result, these amino acids and their byproducts build up in the body. Because this accumulation is toxic to tissues and organs, it leads to the signs and symptoms of maple syrup urine disease.

Infants born with maple syrup urine disease tend to have urine that smells like burnt caramel. These children typically have do not feed well, vomit frequently, are lethargic, and have developmental delays.

Tags: dld gene, maple syrup urine disease, genetics, genes, genome, dna, diseases, illness, health

Chromosome 6 is in focus today as the chromosome parade continues on its way. Among the 1,100 to 1,600 genes on the chromosome is the polycystic kidney and hepatic disease 1 (autosomal recessive) gene also known as the PKHD1 gene at location 6p12.2. Normally, the PKHD1 gene encodes the fibrocystin protein that plays a role in how kidney cells interact with other molecules and cells. Fibrocystin is also a component of primary cilia in the kidney’s renal tubules.

Mutations in the PKHD1 gene have been associated with autosomal recessive polycystic kidney disease.

Polycystic kidney disease is a disorder that affects the kidneys and other organs. Clusters of fluid-filled sacs, called cysts, develop in the kidneys and interfere with their ability to filter waste products from the blood. The growth of cysts causes the kidneys to become enlarged and can lead to kidney failure. Cysts may also develop in other organs, particularly the liver.

Here’s a story in The Journal of friends James Herrell and Doug Miller. James suffers from polycystic kidney disease and has been on dialysis for three years. Today, Doug will donate a kidney to James at Johns Hopkins. Best wishes to them both for a successful surgery!

Tags: pkd, polycystic kidney disease, doug miller, james herrell, chromosome 6, chromosomes, pkhd1 gene, genetics, genes, dna, diseases, illness, health, kidney

The chromosome parade moves along today to chromosome 4 and the huntingtin gene (HD gene) for Huntington disease on 4p16.3. Huntington disease is a “progressive brain disorder that causes uncontrolled movements, mental and emotional problems, and loss of thinking ability (cognition).”

The inherited mutation in the HD gene that causes Huntington disease abnormally repeats the CAG segment from 36 to more than 120 times.

People with 36 to 40 CAG repeats may or may not develop the signs and symptoms of Huntington disease during their lifetime, while people with more than 40 repeats almost always develop the disorder during a normal lifetime.

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Third up in the Genetics and Health chromosome parade is #3 and the gene in focus is Usher syndrome 3A (USH3A). USH3A plays a role in normal vision and hearing, specifically in the synapses between the nerve cells in the inner ear and retina.

What conditions are related to the USH3A gene?

Usher syndrome type III is characterized by progressive hearing loss and vision loss that begin in the first few decades of life

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Marching in our chromosome parade today is chromosome #2 and the gene that’s sitting on the float in the seat of honor is the ectodysplasin A receptor (EDAR) gene involved in determining the formation of body tissues that develop from the ectoderm - skin, hair, nails, and sweat glands. As many as 20 mutations in the EDAR gene have been associated with hypohidrotic ectodermal dysplasia. People with the condition experience:

• Reduced ability to sweat (hypohidrosis) because they have fewer sweat glands than normal or their sweat glands do not function properly.
• Sparse scalp and body hair (hypotrichosis)
• Absent teeth (hypodontia) or malformed teeth
• Distinctive facial features - prominent forehead, thick lips, flattened bridge of nose
• Thin, wrinkled, and dark-colored skin around the eyes
• Chronic skin problems, e.g., eczema
• Foul smelling discharge from the nose (ozena)

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Every Saturday, I’m planning to highlight a disease gene on each of the 24 human chromosomes: 1-22, X, and Y. My resource will be the Genetics Home Reference and I’ll choose whatever catches my eye for the chromosome of the week.

This week, I’m checking out the PSEN2 gene on the long arm of chromsome 1 (1q31-q42). I’ve written about the presenilin genes before and here’s an excerpt from the Genetics Home Reference:

Approximately 11 mutations in the PSEN2 gene have been shown to cause type 4 Alzheimer disease. Mutations in this gene account for less than 5 percent of cases of early-onset familial Alzheimer disease. Two of the most common PSEN2 mutations that cause type 4 Alzheimer disease change one of the building blocks (amino acids) used to make presenilin 2. …These mutations appear to affect the processing of amyloid precursor protein, leading to the increased formation of a protein fragment called amyloid beta peptide. This peptide can form clumps in the brain (amyloid plaques) that are characteristic of Alzheimer disease.

Technorati Tags: chromosomes, chromosome 1, presenilin, psen2, genetics, genes, dna, diseases, illness, health