Medical Genetics: Single-Gene, Enzyme, and Chromosomal Disorders

Flashcards covering key vocabulary, genetic markers, and clinical symptoms for single-gene, metabolic, and chromosomal disorders based on the lecture transcript.

Sickle Cell Anaemia (Genetic Cause)

$Glu6Val$ missense mutation in the $6^{th}$ amino acid of the $\beta$-globin chain.

BCL11A

A modifier gene for Sickle Cell Anaemia that silences $\gamma$-globin synthesis.

Huntington's Disease (Molecular Basis)

$(CAG)_n$ repeat expansion in the coding region of the $HD$ gene on chromosome $4$. Thresholds: normal $9-35$, premutation $36-39$, affected $40+$.

Paternal Transmission Bias

In Huntington's Disease, the condition develops earlier if the mutation is transmitted by an affected father.

Rett Syndrome

An X-linked dominant, male-lethal condition caused by mutations in the $MECP2$ gene, which encodes methyl-CpG-binding protein $2$.

PCDH19 Mutation

Female-Limited Epilepsy and cognitive impairment caused by mosaicism for protocadherin $19$ expression due to random X-inactivation; males are spared due to a different compensating protocadherin.

Leri Weill Dyschondrosteosis

A pseudoautosomal dominant inheritance disorder caused by $SHOX$ gene mutations, characterized by skeletal dysplasia and disproportionate short stature.

Prader-Willi Syndrome

Genomic imprinting disorder on chromosome $15q11.2-q13$ where the abnormality is on the paternal chromosome and the maternal chromosome is inactivated; characterized by childhood obesity and hyperphagia.

Angelman's Syndrome

Genomic imprinting disorder on chromosome $15q11.2-q13$ where the abnormality is on the maternal chromosome and the paternal chromosome is inactivated; characterized by frequent laughter and ataxia.

Fragile X Syndrome (Genetic Cause)

$(CGG)_n$ unstable trinucleotide expansion in the $5'$-UTR of the $FMR1$ gene; causes excessive methylation of CpG islands and gene silencing.

Myotonic Dystrophy

Autosomal dominant condition caused by $(CTG)_n$ unstable repeats in the $3'$-UTR of the $DMPK$ gene; exhibits the Founder Effect in Quebec.

MELAS

Mitochondrial encephalomyopathy characterized by Myopathy, Epilepsy, Lactic Acidosis, and Stroke-like episodes, caused by a maternally inherited point mutation.

Heinz Bodies

Insoluble denatured hemoglobin tetramers that precipitate in red blood cells due to point mutations (e.g., Hb Hammersmith), leading to hemolysis.

Hb Kempsey

A hemoglobin variant with altered oxygen affinity that locks Hb in a high $O_2$-affinity state, reducing delivery to tissues and resulting in polycthemia.

Hydrops fetalis

Homozygous $\alpha$-thalassemia (Hb Bart's: $\gamma_4$) resulting from the loss of all $4$ functional $\alpha$ genes ($0\%$ production).

Classic PKU

Autosomal recessive condition on chromosome $12$ caused by Loss of Function (LOF) mutations in the $PAH$ gene, leading to an absence of phenylalanine hydroxylase.

Molecular Mimicry in Tay-Sach's

Deficiency in $HEX-A$ (hexosaminidase-A) on chromosome $15q.23-24$ leading to the inability to degrade $GM2$ ganglioside.

Gaucher cells

Macrophages engorged with glycolipids (glucocerebroside) in the lysosomes, characteristic of Gaucher's disease ($\beta$-glucocerebrosidase deficiency).

Homocystinuria

A vitamin-responsive disorder (B6, B9, B12) of methionine metabolism typically caused by a defective $CBS$ gene producing cystathionine $\beta$-synthase.

$\alpha1$-antitrypsin deficiency (A1AT)

An ecogenetic disorder caused by $SERPINA1$ mutations (Z-allele) where the lack of $\alpha1$AT fails to inhibit neutrophil elastase, leading to COPD and liver cirrhosis.

PCSK9 Protease

In Familial Hypercholesterolemia, a Gain of Function (GOF) mutation in this protease increases the degradation of LDL receptors, leading to high plasma LDL.

$$\Delta F508$$

The most common Cystic Fibrosis allele, involving a mutation in the $CFTR$ region coding for $NBD1$, leading to a protein trafficking defect.

Gower’s Sign

A clinical symptom of Duchenne Muscular Dystrophy where a child has difficulty rising and must use their hands/support to 'walk up' their own body.

$\epsilon 4$ Allele

An allele of the $APOE$ gene that predisposes individuals to early-onset Alzheimer's Disease and is a major component of amyloid plaques.

Robertsonian Translocation (Familial Down Syndrome)

A translocation typically between chromosome $21q$ and another acrocentric chromosome ($14$ or $22$) that has a high recurrence risk regardless of maternal age.

Williams Syndrome

A microdeletion syndrome at $ch7q11.23$ affecting the $ELN$ (elastin) gene, presenting with elfin-like features and an extremely friendly personality.

Cri du Chat Syndrome

$46,5p-$ deletion involving the $TERT$ gene (telomerase reverse transcriptase), characterized by a cat-like cry at birth and glottis abnormalities.

Klinefelter’s Syndrome

A sex chromosome disorder ($47,XXY$) in males characterized by infertility, small testes, gynecomastia, and tall stature.

Turner Syndrome

A sex chromosome disorder ($45,XO$) in females characterized by short stature, webbed neck, shield chest, and reproductive sterility.