Single Gene Disorders

Examples of Single Gene Disorders

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Last edited and updated on: by Sagar Aryal

Single Gene Disorders

Image Source: A-T Society.

About 10,000 or more single-gene disorders have been identified, which affect approximately 1-2% of the total population. Some of these disorders are as follow:

Huntington disease

The name of the disease is on the name of Dr. George Huntington, who describes this disease in 1872 in North American kindred. It is an autosomal dominant disorder with variable age of onset and anticipation (increasing severity in succeeding generation). The frequency of disease is 1 in 10,000. The main symptom is degeneration (break down) of nerve cells in the brain, cognitive and psychiatric disorder, and movement abnormality. About 5% of Huntington disease is present before the age of 20 years, the average duration of illness is 10-15 years. Juvenile HD is generally paternal with an age of onset. Gene for HD located on 4p16.3.

Myotonic dystrophy

It is the most common form of muscular dystrophy seen in adults with a frequency of 1 in 8000. It shares a common feature with Huntington disease (autosomal dominant inheritance with anticipation). But unlike juvenile Huntington disease, its early onset is exclusively maternal and present at birth. The symptom is not limited exclusively to the neuromuscular system, have also some other features like cataracts, cardiac conduction defect gastro-intestinal defect, etc. Gene located on 19q13.3.

Hereditary Motor and Sensory Neuropathy

It is also called Charcot-Marie-Tooth disease and peroneal muscular atrophy, has a frequency of 1 in 2500. It is two types of HMSN type I and HMSN type II. In type I, motor nerve conduction velocity (MNCV) is reduced nerve biopsies from patients show segmental demyelination accompanied by hypertrophic changes with ‘onion bulb’ formation. In type II MNCV is normal or only slightly reduced and nerve biopsies show axonal degeneration. It can show autosomal dominant, autosomal recessive, or X-linked inheritance. There is an onset of slowly progressive distal muscle weakness and wasting in the lower limbs between the ages of 10 and 30 years

Neurofibromatosis

There are two main types of neurofibromatosis, NF1, and NF2. Both especially NF2 could be included under familial cancer syndromes. NF1 has a birth-rate of 1 in 3000 and NF2 has 1 in 35000. In NF1 symptoms are small pigmented skin lesions, known as café-au-lait (CAL) spots, and small soft fleshy growths known as neurofibromata, other symptoms include macrocephaly and Lisch nodules. Gene for NF1 is mapped on chromosomes 17 and gene for NF2 is mapped on chromosomes 22q.

Marfan syndrome

It is a disorder of fibrous connective tissue mainly defect in type I fibrillin (a glycoprotein encoded by FBN1 gene present on 15q21). Affected individuals are tall than unaffected family members have join laxity. Defect in connective tissue may lead to ectopia lentis and dilatation of the ascending aorta. The pattern of inheritance is autosomal dominant.

Cystic fibrosis

It is an autosomal recessive disorder, very common in Caucasians with a frequency of 1 in 2500. Mostly affect the respiratory system but other organs are also affected. The main symptom is present of thick mucus which leads to the clogged respiratory system, difficulties in breathing and it is difficult to expel mucus with vigorous coughing. It also affects the digestive system. Affected males are sterile due to congenital bilateral absence of vas deferens (CBAVD).

Inherited Cardiac Arrhythmias  and Cardiomyopathies

About 4% of sudden cardiac death are due to Inherited Cardiac Arrhythmias and Cardiomyopathies. Both are genetically heterogeneous but mostly follow autosomal dominant. These are divided into several subtypes each sub-type is due to a particular mutated gene. Mostly death occurs in young males during sleeping or swimming.

Spinal Muscular Atrophy

It is an autosomal recessive disorder with a frequency of 1 in 10,000. Degeneration of anterior horn cells of the spinal cord can lead to progressive muscular weakness and death. It is of three types – Spinal Muscular Atrophy Type I  (Werdnig-Hoffmann Disease), Spinal Muscular Atrophy Type II, Spinal Muscular Atrophy Type III  (Kugelberg-Welander Disease). Type I present on birth or in the first 6 months after birth, type II less severe than type I with age onset of 6-18 month, type III mild form at childhood symptom start to appear after 18 months, all patient walk without support in childhood, slow progression of muscular weakness use of a wheelchair in early adulthood.

Duchenne Muscular Dystrophy

The most common and severe type of muscular dystrophy, a similar but milder form is called Becker muscular dystrophy caused by the same gene mutation. DMD and BMD have a frequency of about 1 in 3500 males and 1 in 20,000 males respectively. Both disease are X-linked recessive, mostly occurs in males. Symptom starts to appear at the age of 3-5 years, most of the affected patients use a wheelchair at the age of 11 years and may lead to death at the age of 18 years. In BMD (mild form) much less aggressive symptoms start to appear at the age of 11 years.

Haemophilia

It is caused by a deficiency of factor VIII and factor IX. Hemophilia is of two types – hemophilia A and hemophilia B. Hemophilia A is due to deficiency of factor VIII and hemophilia B are due to deficiency of factor IX. Factor VIII along with factor IX plays a role in the conversion of prothrombin to thrombin and then thrombin converts fibrinogen to fibrin for coagulation of blood. Due to lack of any one of these factor coagulation of blood does not take place, when the affected person injured coagulation takes very much time and person bleed continuously. Females are mainly carriers due to the presence of two X chromosomes, they have the disease only when both X chromosomes are affected.

Detection of a genetic disorder

The disorder can be detected by prenatal detection through amniocentesis or by other measures. After birth detection takes place after the appearance of symptoms and by karyotyping. In most cases symptoms appear after the onset of age in these cases if there is no prenatal detection, diagnosis of the disease takes after when symptoms appear.

Treatment

By particular protein

The affected person can be treated by the use of a particular type of protein which is defective. Like hemophilia is treated successfully by use of plasma-derived factor VIII and IX, during surgery or major trauma to stop the bleeding with a half-life of 8 hours.

By gene therapy

Gene therapy is an effective treatment, in several cases lead to disease cure or slow down the severity of the symptom.

Reference

  1. Emery’s Element of medical genetics by Peter Turnpenny and Sian Ellard
  2. HUMAN PHYSIOLOGY by Wikibooks contributors
  3. https://www.ncbi.nlm.gov Single-Gene Disorder – Understanding Genetics – NCBI

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