Diseases Flashcards
Achondroplasia
Auto Dominant
- 80% Sporadic Mutation
c. 1138G > A
p. G380R mutation
- Disproportionate Dwarfism
- Lumbar Lordosis
Thanatophoric Dysplasia
Auto Dominant
- Always Sporadic Mutation
- Micromelic Limb shortening
- Frontal Bossing
TD 1 - Curved Femurs, Possible Cloverleaf Skull
TD 2 - Straight Femurs, Cloverleaf Skull
Acute Intermittent Porphyria
Auto Dominant; Haploinsufficiency
Porpholobilinogen Deaminase deficiency
- Wine red urine
- NO PHOTOSENSITIVITY
- worsened by hormones, drugs, and diet
Alzheimer’s Disease
Auto Dominant
Early Onset:
- APP, PSEN 1 OR 2 defect
Late Onset:
- Multifactorial (ApoE 4)
Androgen Insensitivity Syndrome
X-linked Recessive
Mutations in Androgen Receptor Gene
46XY = feminization of male genitalia, female secondary sexual phenotypes, infertility (no ovaries/uterus, but testes may function)
46XX = heterozygous carriers, minimal effect
Note: likely has something to do with SRY
Alpha Thalassemias
# of Genes deleted = form 1 = silent carrier (HbA) 2 = Alpha Thalassemia Trait (HbA w/ minor HbH) 3 = Hemoglobin H disease (HbH aka beta 4; unstable) 4 = Hydrops Fetalis (Hb Barts aka gamma 4)
Beta Thalassemias
Heterozygous = Minor form, mostly asymptomatic
“Leaky Mutation”
Homozygous = Major form aka Cooley’s Anemia
- Null Mutations
- Hepatosplenomegaly
- Iron Overload
Congential Adrenal Hyperplasia
Auto Recessive
Mutations in 21 Hydroxylase (CYP21A2)
- Gene Conversion results in enzyme deficiency
- Female Pseudohermaphroditism
- 46 XX will have genitalia with male characteristics (ambiguous or fully male), but also normal ovarian development
- 46 XY may have hypospadias
Craniofrontonasal Syndrome
X-linked Dominant; Dominant-Negative
Mutations in EFNB1
- Affects women more than men (hemizygosity is better than heterozygosity)
- Groove nose, longitudinal nail split, coronal synostosis
DMD
X-linked Recessive
Null Mutation resulting in complete lack of dystrophin
- Progressive symmetrical muscular weakness (proximal more than distal
- weakened neck flexion against gravity
BMD
X-linked Recessive
In-frame deletion resulting in residual dystrophin activity
- milder presentation and slower progression than DMD
- High variability
- Activity-induced cramping
- neck flexion preserved
Fragile X Syndrome (FRAXA)
X-linked Dominant
CGG expansions in 5’ UTR of FMR1 (2nd leading cause of mental retardation after Down’s Syndrome; Loss of Function)
In Males: Delayed developmental milestones, macroorchidism, strabismus, pes planus
In Females: 50% Penetrance (heterozygotes), same physical and behavioral features as males but with lower frequency and milder involvement
Friedrich Ataxia
Auto Recessive
GAA expansions in Intron 1 of Frataxin (FXN); due to slippage (Loss of Function)
- Anticipation
- Neurodegen
- Muscle weakness, diabetes
Hemophilia A
X-linked Recessive
Defect in Factor 8 (F8 gene)
- Coagulation disorder
- Variable severity: more residual function = milder disease, less residual function = more severe disease
Note: Hemophilia B = defect in Factor 9 (F9 Gene)
Huntington’s Disease
Auto Dominant
CAG repeats of Huntingtin (Gain of Function; Altered Protein)
- Anticipation (expansion in paternal germline)
- Chorea
- Depression
- Cognitive Decline
Myotonic Dystrophy
Auto Dominant
CTG expansion in 3’ UTR of DMPK gene (Gain of Function; altered RNA)
- Anticipation (expansion in female germline)
- Myotonia, muscle wasting, weakness
- Cataract
- Hypogonadism
Nail Patella Syndrome
Auto Dominant
Mutation in LMX1B TF
Pleiotropic
- Nail Dysplasia
- Pterygia/Elbow Dysplasia
- Iliac Horns (Extoses of the Ilia)
- Absent Patella
Osteogenesis Imperfecta
Auto Dominant; Dominant Negative
Type I: Mild (Null Mutation)
Type II: Lethal (Missense)
Type III: Severe (Missense)
Affects Col1A1 or Col1A2 of type 1 collagen
PKU
Auto Recessive
Form of Hyperphenylalaninema
Deficiency of Phenylalanine Hydroxylase
- Mental Retardation
- Mousy Odor
- Hypopigmentation
BH4 Deficiency
Deficiency of BH4 cofactor (for Phenylalanine Hydroxylase)
- Mental Retardation
Prader Willi Syndrome
Neither Recessive nor Dominant
Lack of Paternal contribution of 15q11-13 (SNRPN)
- Moderate Retardation
- Polyphagia, Obesity (Type 2 DM
Angelman Syndrome
Neither Recessive nor Dominant
Lack of Maternal contribution of 15q11-13 (UBE3A)
- Severe Retardation
- Seizures
- Happy Demeanor
- Coarse Facies
Rett Syndrome
X-linked Dominant
Mutations in MEPC2 (Encodes Methyl CpG-Binding Protein 2)
- presents in women more than men.
- hand wringing
- mental retardation
Sickle Cell Disease
Auto Recessive
A -> T mutation in HBB encoding Beta Globin (Glutamic acid -> Valine)
- Severe Hemolysis
- Hemolytic Anemia
- Repeated infections
- occlusion of capillaries (swelling of hands/feet)
