A 40-year-old Caucasian lady presents with depression. Which one of the following genotypes will be associated with better treatment response to SSRIs?
A. It has been demonstrated that the ‘short’ polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) is associated with impaired efficacy of fluvoxamine and paroxetine. The long form is associated with better SSRI efficacy. This can be understood by studying the mechanism of action of SSRIs. SSRIs produce antidepressant action by reducing the activity of serotonin transporter protein. In patients with the short polymorphism of the promoter region, the number of serotonin transporter molecules is reduced, leaving less substrate on which SSRIs can act. Hence the short form is associated with poorer response than the longer form, but this might be confounded by an ethnicity effect as Korean and Japanese patients show the opposite effect (the short version is associated with better SSRI response).
Reference:
A child suffers from moderate learning disability, facial rash, and renal and lung cysts. He has coffee-coloured patches on his skin with intractable seizures.
The mode of inheritance of this disease is:
C. The name tuberous sclerosis comes from the characteristic tuber or potato-like nodules in the brain, which calcify and become sclerotic. The disorder is also known as epiloia or Bourneville’s disease. Though most infants show signs in the first year of life, clinical features can be subtle initially, leading to misdiagnosis for years. The disease-causing mutations are present in either of two genes, TSC1 and TSC2. TSC1 is present on chromosome 9 and produces a protein hamartin. The TSC2 gene is on chromosome 16 and produces a protein tuberin. The natural course is very variable, ranging from mild to severe illness. In addition to the benign tumours of kidney (cysts, angiomyolipomas), phakomas of eyes, cardiac tumours, and brain tumours (tubers, subependymal nodules, and astrocytomas) that frequently occur in tuberous sclerosis, other common symptoms include seizures, mental retardation, behaviour problems, and skin abnormalities. Malignant tumours are rare and occur primarily in the kidneys. An often quoted dermatological triad consists of adenoma sebaceum (facial angiofibromas), ash-leaf macules (hypomelanotic macules), and shagreen patches (pebbly skin on the nape of the neck). Café-au-lait patches and ungual fibromata are other manifestations of tuberous sclerosis. In most patients, tuberous sclerosis is due to a spontaneous new mutation but in those who inherit tuberous sclerosis, the pattern of inheritance is autosomal dominant.
A 21-year-old man with mental retardation and features of autism, enlarged external ears, and protruding jaw is most likely to show which of the following genetic abnormalities?
A. This description fi ts best with fragile-X syndrome. Fragile-X syndrome is also known as Martin–Bell syndrome. It is the most common cause of inherited mental retardation and is the second most common cause of genetically associated mental deficiencies after trisomy 21. Clinical features include mild-to-moderate autism-like behaviour, especially hand flapping and gaze avoidance, attention deficits, and learning disability with an IQ often in the range 35 to 70. Delays in reaching early milestones for speech and language developmental are also noted. Normally, unaffected individuals have 5 to 55 CGG repeats at the 5’ end of locus Xq27.3. A span of 65–200 repeats is known as a premutation, whereas more than 200 repeats is a full mutation. Hypermethylation of cysteine bases takes place at the fully mutant locus, leading to gene inactivation. In trinucleotide expansion diseases, CAG expansion is seen in Huntington’s disease (chromosome 4); CTG expansion is seen in myotonic dystrophy (chromosome 19).
The existence of two or more different mutant alleles at the same locus, resulting in varied clinical expression is called:
A. Allelic heterogeneity is said to be present if different alleles at the same locus produce the same trait or disease expression. Consider sickle cell disease. In this condition all affected individuals carry the same mutation at the same locus. This is called genetic homogeneity. But in cystic fibrosis, at the same site on chromosome 7, 600 various mutations have been identified that result in the same disease phenotype. This is called allelic heterogeneity. Locus heterogeneity refers to a single disorder, trait, or pattern of traits that is caused by mutations in genes at different chromosomal loci.
Which of the following describes the phenomenon that the same gene has two or more different effects?
C. Pleiotropy is a very common phenomenon among genetic diseases. It refers to a single genetic defect producing a variety of defects, in multiple organs in the body, for example Marfan’s syndrome. Here, an autosomal dominant mutation of a gene encoding fibrillin protein leads to a variety of defects, such as lens dislocation, skeletal deformities, and cardiac defects, especially aortic vessel disease.
Click to expand