Block 15 Genetic Pathology

Acrocentric chromosomes are involved in Robertsonian translocations. Robertsonian translocation is a type of chromosomal rearrangement where two non-homologous chromosomes break at their centromeres and the long arms fuse together, forming a single large chromosome. Acrocentric chromosomes have a centromere located close to one end, resulting in a long q arm and a very short p arm. This structure makes them more prone to breakage and fusion, making them commonly involved in Robertsonian translocations.

The given karyotype, 47XY, +21, represents an aneuploid set and trisomy. Aneuploidy refers to an abnormal number of chromosomes, either an extra or missing chromosome. In this case, the presence of an extra chromosome 21 (+21) indicates trisomy 21, which is commonly known as Down syndrome. Trisomy refers to the presence of an extra copy of a chromosome, resulting in a total of three copies instead of the usual two. Therefore, both aneuploid set and trisomy accurately describe the given karyotype.

The correct answer is D. Early loss of oocytes (before puberty). Turner syndrome is a genetic disorder that affects females and is characterized by the absence or abnormality of one of the X chromosomes. This condition can cause the ovaries to not develop properly, leading to a decrease in the number of eggs available for fertilization. As a result, many women with Turner syndrome experience infertility due to the early loss of oocytes, which occurs before puberty. This is a major cause of infertility in individuals with Turner syndrome.

Muscle hypotonia refers to decreased muscle tone, which can result in weak muscle strength and difficulty with movement. Cardiomegaly refers to an enlarged heart. Both of these conditions in infancy are associated with lysosomal accumulation of glycogen. Lysosomes are cellular organelles responsible for breaking down various substances, including glycogen. When there is a defect in the enzymes responsible for breaking down glycogen in lysosomes, glycogen accumulates within the lysosomes, leading to the symptoms of muscle hypotonia and cardiomegaly.

The electron microphotograph shown is characteristic for Tay-Sachs disease. Tay-Sachs disease is a genetic disorder characterized by the accumulation of a fatty substance called GM2 ganglioside in the cells of the brain and nervous system. The electron microphotograph shows the presence of characteristic membranous bodies, known as lamellar bodies, which are a hallmark feature of Tay-Sachs disease. These bodies are formed due to the accumulation of GM2 ganglioside in the lysosomes of cells.

Patients with Marfan syndrome are at an increased risk of developing a dissecting aortic aneurysm and its rupture. This is because the syndrome affects the connective tissue, including the walls of the aorta, making it weaker and more prone to rupture. Additionally, mitral valve prolapse and heart failure are also common causes of death in patients with Marfan syndrome, as the syndrome can affect the structure and function of the heart valves.

Genetic disorders may delay with manifestations till late adulthood because some genetic disorders have a late onset and may not show symptoms until later in life. They may result from spontaneous mutations in gametes because genetic mutations can occur randomly during the formation of reproductive cells. They may also result from spontaneous mutations in embryonic somatic cells because genetic mutations can occur during early stages of development in the embryo.

Cataract in infancy is associated with Galactosemia. Galactosemia is a genetic disorder that affects the body's ability to break down galactose, a sugar found in milk and dairy products. When galactose builds up in the body, it can cause various health problems, including cataracts. Cataracts are clouding of the lens in the eye, leading to blurry vision or vision loss. Therefore, the presence of cataracts in infancy can be an indication of Galactosemia.

Velocardiofacial syndrome (VCFS) is a genetic condition characterized by abnormal pharyngeal arch development that results in defective development of the parathyroid glands, thymus, and conotruncal region of the heart.
Affected individuals may present with structural or functional palatal abnormalities, cardiac defects, unique facial characteristics, hypernasal speech, hypotonia, and defective thymic development.
An estimated 75% of patients with velocardiofacial syndrome have cardiac anomalies. The cardiac defects are usually of the conotruncal type, which occur secondary to abnormal development of the outflow portion of the developing heart. The most common cardiac defects include interrupted aortic arch type B (50%), truncus arteriosus (34.5%) and tetralogy of Fallot (16%). Other cardiac defects include pulmonary atresia with ventricular septal defect, absent pulmonary valve syndrome, ventricular septal defect (especially when accompanied by aortic arch anomalies), aortic stenosis, anomalies of the aortic arch or its major branches, and pulmonary artery anomalies
Palatal abnormalities predispose to speech and feeding difficulties.
The defective thymic development is associated with impaired immune function. This condition not only predisposes to an increased risk of infection but also predisposes some individuals to develop autoimmunity. Parathyroid and immune deficiencies can progress or resolve with time.
In addition, affected individuals may present with learning disabilities, overt developmental delay, psychiatric disorders, and renal and musculoskeletal defects.
Ophthalmologic abnormalities are seen in 70% of patients with velocardiofacial syndrome, such as posterior embryotoxon, bilateral cataracts, tortuous retinal vessels, and small optic disks. Other rare anomalies include congenital absence of the nasolacrimal duct.
About 10% of patients with velocardiofacial syndrome have DIGEORGE SYNDROME, which consists of at least 2 of the following features:
• Conotruncal cardiac anomaly
• Hypoparathyroidism, hypocalcemia
• Thymic aplasia, immune deficiency
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Gaucher disease is a genetic disorder that affects the metabolism of certain fats in the body. It is caused by a deficiency of an enzyme called glucocerebrosidase. While Gaucher disease can cause a range of symptoms, including enlarged liver and spleen, anemia, and bone problems, the life span of individuals with Gaucher disease is not affected. With proper management and treatment, individuals with Gaucher disease can live a normal life span.

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Balanced translocations can have medical significance as they can lead to various outcomes. They may cause neoplastic growth, which refers to the formation of tumors or cancerous cells. Additionally, they may cause partial aneuploidy in offspring, meaning there is an abnormal number of chromosomes in some cells. This can result in developmental abnormalities or genetic disorders. It is important to note that while these outcomes are possible, not all balanced translocations will necessarily lead to these effects.

Salty sweat in patients with CF is associated with CFTR mutation because CFTR is a protein that regulates the movement of chloride ions across cell membranes, including those in sweat glands. When CFTR is mutated, it leads to a defective chloride channel, causing an imbalance of ions in sweat and resulting in salty sweat. Inhibition of ENaC is also associated with salty sweat in CF patients because ENaC is a sodium channel that is overactive in CF, leading to excessive reabsorption of sodium and water in sweat glands, which further increases the saltiness of sweat.

Patients with Klinefelter syndrome may experience azoospermia, which means they have no sperm in their ejaculate. Additionally, their testicles may undergo atrophy, meaning they become smaller and less functional. These two conditions can contribute to infertility in individuals with Klinefelter syndrome.

Gaucher's disease is a genetic disease in which a fatty substance (lipid) accumulates in cells and certain organs. Gaucher's disease is the most common of the lysosomal storage diseases. It is a form of sphingolipidosis (a subgroup of lysosomal storage diseases), as it involves dysfunctional metabolism of sphingolipids. The disorder is characterized by bruising, fatigue, anemia, low blood platelets, and enlargement of the liver and spleen. It is caused by a hereditary deficiency of the enzyme glucosylceramidase. The enzyme acts on the fatty acid glucosylceramide. When the enzyme is defective, glucosylceramide accumulates, particularly in white blood cells, most often macrophages (mononuclear leukocytes). Glucosylceramidase can collect in the spleen, liver, kidneys, lungs, brain and bone marrow.
Symptoms may include enlarged spleen and liver, liver malfunction, skeletal disorders and bone lesions that may be painful, severe neurologic complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin, anemia, low blood platelets and yellow fatty deposits on the white of the eye (sclera). Persons affected most seriously may also be more susceptible to infection. Some forms of Gaucher's disease may be treated with enzyme replacement therapy.
The disease is caused by a recessive mutation in a gene located on chromosome 1 and affects both males and females. About 1 in 100 people in the United States are carriers of the most common type of Gaucher disease. The carrier rate among Ashkenazi Jews is 8.9% while the birth incidence is 1 in 450

Trisomy 16 is a chromosomal abnormality in which there are 3 copies of chromosome 16 rather than two. It is the most common trisomy leading to miscarriage and the second most common chromosomal cause of it, closely following X-chromosome monosomy. Like most chromosomal abnormalities, trisomy 16 usually causes miscarriage in the first trimester of pregnancy.
It is not possible for a child to be born alive with an extra copy of this chromosome present in all cells (called Full Trisomy 16). It is possible for a child to be born alive with the mosaic form
Despite the excellent postnatal prognosis, 99% of Turner-syndrome conceptions are thought to end in spontaneous abortion or stillbirth, and as many as 15% of all spontaneous abortions have the X,O karyotype

The development of azoospermia in Klinefelter syndrome can be attributed to the following conditions: low androgen receptor (AR) response to testosterone and dihydrotestosterone, as well as extended CAG repeats in the AR gene. These conditions can affect the normal functioning of the androgen receptor, leading to impaired sperm production and ultimately azoospermia.

The correct answer is that Prader-Willi syndrome develops when the PW gene is imprinted on the paternal chromosome, the PW gene on the paternal chromosome is lost, and both 15th chromosomes are maternal. This means that the genes responsible for regulating appetite and hunger are affected, leading to excessive hunger and overeating, as well as other symptoms associated with Prader-Willi syndrome.