MENDELIAN DISORDERS Flashcards
Mutation in single gene with large effects
Mendelian Disorders
True or False:
In mendelian disorders, Each person carries 5-8 deleterious genes but recessive that does not result to serious phenotypic abnormalities
True
Three patterns of transmittance
- autosomal dominant
- autosomal recessive
- x-linked (sex linked)
It is expressed in mathematical terms
Penetrance
True or False:
50% penetrance indicates that 50% of those who carry the gene express the trait
True
If a trait is seen in all individuals carrying the mutant gene but is expressed differently among individuals, the phenomenon is called ____________
Variable expressivity
True or False:
In autosomal dominant, only one allele is needed to manifest
True
Origin of autosomal dominant
Some are de novo; manifested in HETEROZYGOUS
Origin of autosomal recessive
Do not affect the parents, may manifest in sibling; HOMOZYGOUS
True or False
In autosomal recessive, two alleles are needed to manifest
True
Origin of X-Linked
Almost all are recessive
Clinical features of autosomal dominant
modified by variation in PENETRANCE and EXPRESSIVITY; M=F
Clinical features of autosomal recessive
more uniform expression, commonly with complete penetrance
Clinical features of x-linked
expressed in males
Age of onset in autosomal dominant
delayed
age of onset in autosomal recessive
early
age of onset in x-linked
any time, depend on disease
Type of proteins involved in autosomal dominant
non-enzyme proteins; membrane receptors and structural proteins
Type of proteins involved in autosomal recessive
enzyme proteins
Type of proteins involved in x-linked
enzyme or structural proteins
type of mutation in autosomal dominant
deletion, point, missense mutation; LOF, GOF
Type of mutation in autosomal recessive
Splice-site, frameshift, point mutation, deletion, non-functional,
misfolded protein
type of mutation in x-linked
Deletions, insertions, non-sense
mutations
Example of disorders in AUTOSOMAL DOMINANT
→ Marfan syndrome
→ Ehlers-Danlos
→ Familial Hypercholesterolemia
→ Hereditary Spherocytosis
Example of disorders in AUTOSOMAL RECESSIVE
→ Cystic fibrosis
→ Glycogenosis
→ Lysosomal Storage Disease
→ Mucopolysaccharidosis
Examples of disorders in X-LINKED
→ Duchene Muscular Dystrophy
→ Fragile X Syndrome
→ Hemophilia A and B
There can be about 600 mutations, mostly missense. Involving FBNI gene or Fibrillin-I gene,
encoding fibrillin I protein.
AD- MARFAN SYNDROME
it is a component of microfibrils which provides skeleton on which
tropoelastin is deposited to form elastic fibers in various tissues of the body like the aorta, ligaments and ciliary zonules of the eye
Fibrillin I protein
Common finding for individuals with Marfan Syndrome
lalagpas yung first digit, the thumb, sa kabilang side.
He is an individual with Marfan Syndrome
Abraham Lincoln
Diagnosis for Marfan Syndrome
Clinical
Lens dislocation
echocardiography
True or False:
Ehlers-Danlos Syndrome is a disorder than encompasses the three patterns of transmittance. They can be transmitted through AR fashion, or sex as a sex-linked disorder
True
Common variants of EDS
o COL5A1 and COL5A2 – classical EDS,
Type I and II
o COL3A1 – Vascular type, type IV
o COL1A1 and COL1A2 –arthrochalasia, type VII a, b
It may be caused by mutations involving structural proteins or enzymes
EDS
Common manifestations involve in EDS
o Skin (hyperextensibility)
o Ligaments
o Joints (hypermobility)
1:2,500 livebirths, carrier rate of 1:20. It is also called Mucoviscidosis. it is the most common lethal genetic diseases affecting Caucasians
AR- CYSTIC FIBROSIS
This gene regulates Cl channel, K channel, ENaC, gap junction channel and cellular
CFTR (Cystic fibrosis transmembrane conductance regulator)
A disorder of ion transport in epithelial cells of exocrine glands and lining epithelial cell of the
respiratory, GI and reproductive tracts
AR- CYSTIC FIBROSIS
What is the gold standard in the diagnosis of mucoviscidosis?
DNA sequencing/ gene sequencing
Hereditary deficiency of one of the enzymes involved in glycogen synthesis or degradation
AR- GLYCOGENOSIS
Three subgroups of glycogenosis
o Hepatic
o Myopathic
o Glycogen
Individuals with ____________ has deficiency of glucose-6-phosphatase
Hepatic Forms
enlargement of heart
cardiomegaly
It is the deletion of Xp21
SLD- DUCHENE MUSCULAR DYSTROPHY
muscles that are the first to weaken in duchene muscular dystrophy
pelvic girdle muscles
Disease that is closely associated to Duchene Muscular Dystrophy
Becker Muscular Dystrophy
Second leading cause of mental retardation and is the primary cause of inherited mental retardation
SLD- FRAGILE X SYNDROME
In Fragile X syndrome, the break or gap is the X chromosome is due to:
CGG sequence
True or False
A normal transmitting male and carrier female have 55-200 repeats (pre-mutations) whereas affected individuals, 200-4000 repeats (full
mutation)
True
True or False:
Clinical features of fragile X syndrome worsen with each generation (anticipation)
True
