Which type IV collagen gene is most likely to be mutated in a family with X-linked Alport syndrome?

Abstract. Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease.

What is COL4A1 mutation?

COL4A1 is a gene encoding the type IV collagen alpha 1 chain, and it is already recognized that mutations in the gene can cause autosomal-dominant porencephaly and infantile hemiparesis. 4,5. Recently, COL4A1 mutations have been identified in adult patients presenting with SVD.

What is Goulds syndrome?

Gould Syndrome is often characterized by abnormal blood vessels in the brain (cerebral vasculature defects), eye development defects (ocular dysgenesis), muscle disease (myopathy), and kidney abnormalities (renal pathology); however, many other aspects of the syndrome including abnormalities affecting the structure of …

Is Alport syndrome autosomal recessive?

Autosomal recessive Alport syndrome is caused by disease-causing variants in both copies of either the COL4A3 or the COL4A4 genes. Autosomes are the non-sex chromosomes that carry most of our genes.

Can Alport syndrome skip a generation?

X-linked Alport syndrome is underdiagnosed in women. The generation skipping observed in X-linked families reflects the presence of undiagnosed women. This occurs because female relatives of affected men are not systematically screened in adult nephrology practice.

Can Alport syndrome cause heart problems?

Severe cases of Alport syndrome are characterized by a high risk of fatal arrhythmias, hyperkalaemic cardiac arrest, heart failure and intraoperative bleeding.

Where is type IV collagen found?

Type IV collagen is a type of collagen found primarily in the skin within the basement membrane zone. The type IV collagen C4 domain at the C-terminus is not removed in post-translational processing, and the fibers are thus link head-to-head, rather than in a parallel fashion.

Does small vessel disease cause headaches?

Affected individuals may also experience seizures and migraine headaches accompanied by visual sensations known as auras. Some people with COL4A1-related brain small-vessel disease have an eye abnormality called Axenfeld-Rieger anomaly.

What is the life expectancy of someone with Alport syndrome?

Prognosis of Alport syndrome Most men with Alport syndrome reach end-stage kidney disease and kidney failure by their 40s or 50s, which can reduce lifespan if not managed with dialysis or a kidney transplant. Most women with Alport syndrome have a normal lifespan.

Is Alport syndrome more common in males or females?

More women are affected than men in X-linked Alport syndrome. Families of offspring of a male (A) and a female (B) with X-linked Alport syndrome demonstrating more affected females than males in their combined offspring (three times as many, 3:1 in one generation; and overall twice as many, 4:2 in the two generations).

How bad is Alport syndrome?

Alport syndrome is a genetic disorder affecting around 1 in 5,000-10,000 children, characterized by glomerulonephritis, end-stage kidney disease, and hearing loss. Alport syndrome can also affect the eyes, though the changes do not usually affect sight, except when changes to the lens occur in later life.

How serious is Alport syndrome?

Alport syndrome is a disease that damages the tiny blood vessels in your kidneys. It can lead to kidney disease and kidney failure. It can also cause hearing loss and problems within the eyes. Alport syndrome causes damage to your kidneys by attacking the glomeruli.

What kind of mutations are found in COL4A5?

These patients have mutations in the COL4A5gene, which encodes the type IV collagen-α5 [α5(IV)] chain. COL4A5mutations result in abnormal α5(IV) expression, with a typically complete absence of α5(IV) in the glomerular basement membrane (GBM) and Bowman’s capsule in men and a mosaic expression pattern in women (1).

How are mutations in COL4A1 related to porencephaly?

Mutations in COL4A1 have recently been identified in both a mouse model and families with porencephaly, a rare autosomal dominant condition characterized by cystic brain cavities and cerebral white-matter lesions. 3-6 COL4A1 mutations have also been found in a single family with small-vessel disease affecting the brain and the eye. 6,7

What kind of angiopathy does COL4A1 cause?

The systemic angiopathy of the HANAC syndrome appears to affect both small vessels and large arteries. COL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps.

Can a mutation in collagen IV cause Alport syndrome?

Mutations to the genes coding for collagen IV lead to Alport syndrome. This will cause thinning and splitting of the glomerular basement membrane. It will present as isolated hematuria, sensorineural hearing loss, and ocular disturbances and is passed on genetically, usually in an X-linked manner, although there are rarer autosomal forms.