[01.03b] Principles of Genetics & Overview of Genetic Pathology (Part 2)

Meiotic nondisjunction

What is the most common cause of Trisomy 21 (Down Syndrome)?

FISH and karyotyping

What are the diagnostic tools used to confirm Trisomy 21?

Maternal origin

Where does the extra chromosome in Trisomy 21 usually come from?

45,X or Turner Syndrome

What is the most common sex chromosome abnormality in females?

Thymic hypoplasia

What is the hallmark feature of DiGeorge Syndrome?

Chromosome 22q11.2 deletion

What chromosomal abnormality causes DiGeorge and Velocardiofacial Syndrome?

Trisomy 13 (Patau Syndrome)

Which chromosomal disorder presents with polydactyly and cleft lip/palate?

Trisomy 18 (Edwards Syndrome)

Which trisomy is associated with rockerbottom feet and horseshoe kidney?

Mosaicism

What causes milder phenotypes in 1% of Down Syndrome cases?

Hypogonadism

What is the consistent feature of Klinefelter Syndrome?

XXY

What is the most common karyotype for Klinefelter Syndrome?

45,X or 45,X0

What is the typical karyotype in Turner Syndrome?

Cystic hygroma

What neck swelling is characteristic of Turner Syndrome?

Primary amenorrhea

What reproductive issue is most associated with Turner Syndrome?

SRY gene

What gene determines male sex on the Y chromosome?

Barr body

What structure represents an inactivated X chromosome in females?

Lyonization

What process results in the inactivation of one X chromosome in females?

Long face, large mandible, macro-orchidism

What are the physical features of Fragile X Syndrome?

CGG repeat on FMR1 gene

What is the trinucleotide mutation in Fragile X Syndrome?

Mental retardation (IQ 20-60)

What is the neurological hallmark of Fragile X Syndrome in males?

Southern blot, PCR, karyotyping

What tests diagnose Fragile X Syndrome?

Oogenesis

When does CGG repeat expansion occur in Fragile X Syndrome?

Fragile X-associated primary ovarian failure

What condition presents with early menopause and high FSH in premutation carriers?

Fragile X-associated tremor/ataxia syndrome

What condition in males causes tremor and may progress to Parkinsonism?

Maternal inheritance

How are mitochondrial disorders transmitted?

Leber Hereditary Optic Neuropathy (LHON)

What mitochondrial disorder causes progressive central vision loss in young males?

Central vision

Where does vision loss start in Leber Hereditary Optic Neuropathy?

Heteroplasmy

What is the presence of both normal and mutant mitochondrial DNA called?

Threshold effect

What term describes the minimum number of mutated mtDNA needed to cause disease?

Genomic imprinting

What process causes functional differences between maternal and paternal alleles?

Prader-Willi Syndrome

Which imprinting disorder is due to a deletion in the paternal chromosome 15?

Angelman Syndrome

Which imprinting disorder results from a deletion in the maternal chromosome 15?

Uniparental disomy

What inheritance involves both chromosome 15s from one parent only?

Mental retardation and hyperphagia

What are common features of Prader-Willi Syndrome?

“Happy puppets” appearance

What is the hallmark behavior in Angelman Syndrome?

Osteogenesis imperfecta

What disorder is often associated with gonadal mosaicism?

Postzygotic mutation in gonads

What causes gonadal mosaicism in phenotypically normal parents?

Advanced maternal age

What is a major indication for prenatal testing of inherited genetic alterations?

Targeted therapy

What cancer treatment strategy is guided by specific tumor mutations?

FISH (Fluorescence in situ hybridization)

What diagnostic test uses fluorescent probes to detect chromosomal abnormalities?

Trastuzumab

What drug targets HER2 amplification in breast cancer?

PCR (Polymerase Chain Reaction)

What test amplifies DNA fragments to detect mutations?

Next Generation Sequencing (NGS)

What modern sequencing method allows massive parallel DNA sequencing?

Sanger sequencing

What original DNA sequencing method is more labor-intensive than NGS?

Cytogenomic array technology

What technique detects chromosomal gains/losses not visible via karyotyping?

RNA analysis

What technique is useful for detecting gene expression or splicing defects?

Mental retardation and obesity

What are hallmark features of Prader-Willi Syndrome?

Hypocalcemia

What electrolyte disturbance is seen in DiGeorge Syndrome due to parathyroid hypoplasia?

Epicanthic folds and simian crease

What facial features are seen in Down Syndrome?

Ring chromosomes and Robertsonian translocations

What are severe chromosomal rearrangements seen in Trisomy 21?