49 Year 2: Molecular Genetics and Cytogenetics exam questions on SINGLE-GENE DISORDERS WITH ATYPICAL INHERITANCE MCQs for medical students. Includes MCQs, answe
This MCQ set contains 49 questions on SINGLE-GENE DISORDERS WITH ATYPICAL INHERITANCE MCQs in the Year 2: Molecular Genetics and Cytogenetics unit. Each question includes the correct answer and a detailed explanation for active recall and exam preparation.
Correct answer: B – Fragile X syndrome
Fragile X syndrome is the second most common genetic cause of mental retardation after Down syndrome, with a frequency of 1 in 1550 for affected males and 1 in 8000 for affected females.
Correct answer: B – Around 29
In the normal population, the number of CGG repeats in the FMR1 gene averages around 29, whereas affected persons have 200 to 4000 repeats (full mutations).
Correct answer: C – 52-200 CGG repeats
Premutations are characterized by 52 to 200 CGG repeats. Carrier males and females have premutations that can be converted to full mutations (200-4000 repeats) during oogenesis.
Correct answer: B – Oogenesis only
During oogenesis (but not spermatogenesis), premutations can be converted to full mutations by further amplification of CGG repeats, which can then be transmitted to both sons and daughters.
Correct answer: C – Macroorchidism
The only distinctive physical abnormality that can be detected in at least 90% of postpubertal males with fragile X syndrome is macroorchidism (large testicles).
Correct answer: B – Anticipation
Anticipation refers to the phenomenon whereby clinical features worsen with each successive generation, as the mutation becomes increasingly deleterious as it is transmitted through generations.
Correct answer: C – 30-50%
From 30% to 50% of carrier females are affected (mentally retarded), a number much higher than that for other X-linked recessive disorders, explained by inheritance of full mutations.
Correct answer: B – Silencing of FMRP due to methylation
When CGG repeats exceed 230, the DNA of the FMR1 gene becomes abnormally methylated, extending to the promoter region, resulting in transcriptional suppression and absence of FMRP.
Correct answer: B – RNA-binding protein that regulates mRNA translation in synapses
FMRP is an RNA-binding protein transported from cytoplasm to nucleus, where it binds specific mRNAs and transports them to axons and dendrites, regulating translation at synapses.
Correct answer: B – Premature ovarian failure before age 40
Approximately 30% of females carrying the premutation have premature ovarian failure (before age 40), indicating that premutations are not benign though abnormalities are milder.
Correct answer: C – Fragile X-associated tremor-ataxia
About one-third of premutation-carrying males exhibit fragile X-associated tremor-ataxia starting in their sixth decade, characterized by intention tremors and cerebellar ataxia, potentially progressing to parkinsonism.
Correct answer: B – During spermatogenesis
Unlike fragile X syndrome where expansion occurs during oogenesis, in Huntington disease and some other trinucleotide repeat disorders, premutations are converted to full mutations during spermatogenesis.
Correct answer: B – Toxic gain of function
When mutations affect coding regions (like in Huntington disease), they give rise to misfolded proteins that interfere with normal protein function, called toxic gain-of-function mutations.
Correct answer: B – Polyglutamine diseases
Diseases involving CAG repeats that encode polyglutamine tracts are referred to as "polyglutamine diseases," which primarily affect the nervous system and feature accumulation of misfolded protein aggregates.
Correct answer: B – Ova contain mitochondria while spermatozoa contain few or none
Ova contain mitochondria within their abundant cytoplasm, whereas spermatozoa contain few if any mitochondria. The mitochondrial DNA of the zygote is therefore derived entirely from the ovum.
Correct answer: C – Skeletal muscle, heart, and brain
Because mitochondrial DNA encodes enzymes for oxidative phosphorylation, diseases from mitochondrial mutations affect organs most dependent on oxidative phosphorylation: skeletal muscle, heart, and brain.
Correct answer: B – Leber hereditary optic neuropathy
Leber hereditary optic neuropathy is the prototypical mitochondrial disorder, manifesting as progressive bilateral loss of central vision leading to blindness.
Correct answer: B – Differential inactivation of genes during gametogenesis
Genomic imprinting is an epigenetic process whereby certain genes are differentially inactivated during paternal and maternal gametogenesis, creating functional differences between maternal and paternal gene copies.
Correct answer: B – Methylation of gene promoter
At the molecular level, imprinting is associated with methylation of the gene promoter, as well as histone protein modifications, which silence the gene.
Correct answer: A – Chromosome 15q11-q13
Both Prader-Willi and Angelman syndromes involve deletion of band q12 in the long arm of chromosome 15 (15q11-q13), but the parent of origin differs.
Correct answer: B – Paternal
In Prader-Willi syndrome, the deletion affects the paternally derived chromosome 15 in all cases, demonstrating parent-of-origin effects on gene function.
Correct answer: B – Mental retardation, obesity, small hands/feet, hypogonadism
Prader-Willi syndrome is characterized by mental retardation, short stature, hypotonia, obesity, small hands and feet, and hypogonadism.
Correct answer: A – Maternal
In Angelman syndrome, the deletion affects the maternally derived chromosome 15, in contrast to Prader-Willi syndrome where the paternal chromosome is deleted.
Correct answer: B – Mental retardation, ataxic gait, seizures, inappropriate laughter
Angelman syndrome patients are mentally retarded and present with ataxic gait, seizures, and inappropriate laughter, giving rise to the name "happy puppet syndrome."
Correct answer: B – Inheritance of both chromosomes of a pair from one parent
Uniparental disomy is the inheritance of both chromosomes of a pair from one parent. In Prader-Willi syndrome, this can occur when both copies of chromosome 15 are from the mother.