Mendelian Disorders I – Key Vocabulary

Vocabulary flashcards summarizing essential terms and definitions from the lecture on Mendelian disorders, autosomal patterns, and detailed sickle cell disease pathophysiology.

Mendelian Disorders

Diseases produced by single-gene mutations that follow classic inheritance patterns: autosomal dominant, autosomal recessive, or X-linked.

Autosomal Dominant Inheritance

Pattern where a single mutant allele on an autosome causes disease; expressed in heterozygotes and often seen in successive generations.

Autosomal Recessive Inheritance

Pattern requiring mutant alleles on both autosomes; carriers are phenotypically normal, and each child of carrier parents has a 25 % risk.

X-linked Recessive Inheritance

Disorders carried on the X chromosome; expressed in hemizygous males, while heterozygous females are usually carriers.

Codominance

Situation in which both alleles of a gene pair are fully expressed in the heterozygote (e.g., ABO blood groups).

Pleiotropism

A single mutant gene producing multiple, seemingly unrelated clinical effects (e.g., sickle cell disease affecting blood, bone, and spleen).

Genetic Heterogeneity

A single clinical disorder produced by mutations in different genes (e.g., childhood deafness linked to ≥ 16 genes).

Reduced Penetrance

Not all individuals with a mutant allele show the phenotype; expressed as a percentage (e.g., 50 % penetrance).

Variable Expressivity

All mutation carriers show the trait, but its severity or features differ among individuals.

Loss-of-Function Mutation

Mutation that reduces or abolishes a protein’s activity, commonly affecting non-enzymatic structural or regulatory proteins.

Gain-of-Function Mutation

Mutation conferring new, often toxic properties on a protein, as in Huntington disease.

Familial Hypercholesterolemia

Autosomal dominant disorder caused by LDL-receptor loss-of-function leading to high cholesterol and premature atherosclerosis.

Osteogenesis Imperfecta

Autosomal dominant collagen defect causing brittle bones and blue sclerae.

Huntington Disease

Autosomal dominant neurodegenerative disorder from CAG repeat expansion; mutant huntingtin is toxic to neurons.

Sickle Cell Disease (SCD)

Group of disorders in which the HbS gene is inherited with another abnormal β-globin gene (e.g., HbSS, HbSC).

Hemoglobin S (HbS)

Abnormal β-globin with valine substituting glutamate at position 6; predisposes deoxygenated Hb to polymerize.

β6 Glu→Val Point Mutation

Single nucleotide change in the β-globin gene replacing glutamic acid with valine, producing HbS.

Polymerization of HbS

Process where deoxygenated HbS molecules aggregate, distorting RBCs into sickle shapes.

Sickling

Reversible or irreversible deformation of RBCs into crescent shapes, reducing deformability and causing membrane damage.

Vaso-Occlusive Crisis

Painful episode caused by microvascular blockage of sickled RBCs leading to tissue infarction and severe pain.

Bone Pain (Dactylitis)

Hand-foot syndrome in children with SCD; painful swelling of small bones during vaso-occlusive crises.

Acute Chest Syndrome

Life-threatening vaso-occlusive crisis in lungs presenting with fever, chest pain, infiltrates, and hypoxia.

Stroke in SCD

Cerebral infarction due to endothelial adhesion of sickled cells and nitric-oxide–mediated vasoconstriction.

Sequestration Crisis

Rapid pooling of sickled RBCs in spleen or liver causing hypovolemia and possible shock, mainly in children.

Aplastic Crisis

Transient cessation of erythropoiesis, usually from parvovirus B19 infection, leading to sudden severe anemia.

Chronic Hypoxia

Persistent low oxygen causing growth retardation and organ damage (spleen, heart, kidneys, lungs) in SCD.

Autosplenectomy

Progressive fibrosis and shrinkage of spleen from repeated infarction, leaving only a fibrous nubbin by adulthood.

Hyposthenuria

Inability to concentrate urine due to medullary sickling, increasing dehydration risk in SCD patients.

Hydroxyurea

Drug that raises HbF levels and decreases leukocyte count, reducing sickling and inflammation in SCD.

Hemoglobin Electrophoresis

Laboratory test separating hemoglobin variants; definitive for detecting HbS or distinguishing HbSC, HbS-β-thalassemia.

Metabisulfite Sickling Test

Induces deoxygenation in vitro; presence of HbS causes RBC sickling visible under the microscope.

Hereditary Persistence of Fetal Hemoglobin (HPFH)

Benign condition with sustained high HbF that ameliorates severity of sickle cell disease.

Hand-Foot Syndrome

Synonym for dactylitis; swelling and pain of hands/feet in infants with SCD during bone infarction.

Consanguinity

Marriage between biologically related individuals, increasing risk of autosomal recessive disorders.

Inborn Error of Metabolism

Genetically determined enzyme defect, most often inherited as autosomal recessive (e.g., phenylketonuria).

Hemizygous

Having only one copy of a gene rather than a pair; applies to X-linked genes in males.

Lyonization

Random inactivation of one X chromosome in female cells, possibly leading to partial expression of X-linked traits.

Glucose-6-Phosphate Dehydrogenase Deficiency

X-linked recessive enzyme defect causing hemolytic anemia after oxidative stress.

Hemophilia A

X-linked recessive deficiency of clotting factor VIII leading to bleeding diathesis.

Familial Polyposis Coli

Autosomal dominant disorder with numerous colon adenomatous polyps and high cancer risk.

Marfan Syndrome

Autosomal dominant fibrillin-1 defect causing tall stature, lens dislocation, and aortic aneurysms.

Polycystic Kidney Disease (ADPKD)

Autosomal dominant disorder with bilateral renal cysts leading to renal failure in adulthood.