Genetic Diseases Flashcards
Obliterated pulp chamber
Dentinogenesis
Soap bubble lucencies are characteristics of ______
Cherubism
______ is the most common form of skin cancer
Basal cell carcinoma
- Multiple, early-onset basal cell carcinomas
- Multiple odontogenic keratocysts of the jaws
- Skeletal anomalies (eg, bifid ribs)
- Enlarged calvarium
- Calcified falx cerebri
- Mild hypertelorism
- Palmar/plantar pits
Nevoid Basal Cell Carcinoma Syndrome
Are hereditary and congenital diseases the same thing?
No
= genetically transmitted from parent to child
Hereditary
_____= synonym for hereditary
Familial
= present at birth–Has nothing to do with transmitting genes from parent to child.
Congenital
A ______ is an organized structure of DNA and protein that consists of a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences.
chromosome
______ formed when a cell needs to duplicate genetic material
Chromosomes
- An image of the metaphase chromosomes
- Reveals the karyotype
- Detects large abnormalities in chromosomes (duplications, deletions, translocations)
- Cannot detect single gene mutations
Karyogram
How many chromosomes are in the human karyotype?
46 chromosomes
An individual has two or more cell populations with a different chromosomal makeup
Chromosomal mosaicism
The genetic makeup
Genotype
The physical manifestation of a disease
Phenotype
_______= there is one copy of a gene (
Hemizygous
______ number: 23 (germ cells: oocytes and spermatocytes)
Haploid
______ number: 46 (all somatic cells)
Diploid
______: A multiple of the haploid number, greater than two (e.g. 69, 92)
Polyploid
______: A karyotype that is not an exact multiple of the haploid number (e.g. 45 or 47)
Aneuploid
- Female has a double dose of genetic material on the X chromosome
- Random inactivation of the X chromosome =
- Inactivated X chromosome presents as the Barr body
- Female is a mosaic with respect to the X chromosome
Lyonization
•In the _____, there are two alleles for genes on the X chromosome–X-linked disease is mild or non-existent in the
female
•In the ____, there is one allele for genes on the X chromosome–X-linked disease is all or none in the
male
- Failure of a homologous chromosome pair to separate during meiosis
- One gamete receives an extra chromosometrisomy
- The other gamete is missing a chromosomemonosomy
Nondisjunction
Females are less severely affected by sex-linked diseases than males due to: A. Lyonization B. Non-dysjunction C. Mosaicism D. Germ line mutations
A. Lyonization
A ______ is a permanent change in the normal base pair sequence
mutation
- A permanent change in the normal base pair sequence
* Can’t be seen on the karyogram
Mutations
______ mutation–a single base pair change causes the substitution of one amino acid for another in the protein
•Mis-sense mutation
______ mutation-results in a stop codon that truncates the protein
•Nonsense mutation
_______ mutation-addition or loss of a nucleotide / nucleotides -changes the reading frame, producing an entirely different amino acid sequence nonfunctional protein
-most damaging
•Frame shift mutation
•A single base pair change causes the substitution of one amino acid for another in the protein–May be no phenotypic effect–Or, the phenotypic effect may be life-threatening:e.g. Sickle cell anemia –a single amino acid substitution of valine for glutamic acid
Missense mutations
•A single base pair change causes the substitution of one amino acid for resulting in a STOP codon that truncates the protein
Nonsense mutations
•Addition or loss of a nucleotide or nucleotides changes the reading frame from the site of the mutation
produces an entirely different amino acid sequence
results in a nonfunctional protein
•Potentially more harmful than a mis-sense mutation
Frameshift mutation
______ mutation
–Present in germ cells (the oocyte and spermatocyte)
–Therefore, present in every cell in the body forever
–Passed on to future generations
•Germ line mutation
______ mutation
–Post-zygotic mutation
–The number of cells bearing the mutation depends on how far into embryogenesis the mutation occurs
–Not passed on to future generations
•Somatic cell mutation
Can you see chromosome abnormalities on karyograms?
Yes
Can you see gene mutations on karyograms?
No
- Phenotype: epicanthal folds, low-set ears, macroglossia, broad nasal bridge, simian crease
- Increased maternal age
- Nondisjunction
Down syndrome
Trisomy 21 is _____
Down syndrome
Do younger or older women have a greater risk of having a child with down syndrome?
Older women
Clinical aspects of ______
•Congenital heart disease: valvular and septal defects40%
•Acute leukemia: 10x -20x increased risk•Infection: Increased risk for infection
•Dementia : Alzheimer-like dementia by age 40
Down syndrome
- Genotype –45, X
- Monosomy for the X chromosome
- AKA Gonadal dysgenesis (sterile)
- Webbed neck
- Cubitus valgus
Turner Syndrome
- Affects only males
- 47, XXY genotype
- Common–1:700
- Phenotype: narrow shoulders, broad hips, variable gynecomastia, normal mental status, sterile
Klinefelter Syndrome
•Additive effect of multiple genes of small effect–Environmental, non-genetic influences
•Multifactorial inheritance fall on a continuous distributionphenotype
•Threshold effect:
–Disorder becomes manifest only when the liability due to genes and environment is exceeded.
•E.g. Alzheimer disease, Colon cancer, Breast cancer, Ovarian cancer, Hypothyroidism, Cleft lip and palate
–Also height, weight,blood pressure, hair color
Multifactorial (Polygenic) Inheritance
–A single copy of the mutant gene produces the disease
Dominant:
–Disease isn’t present with a single copy of the mutant gene Two gene copies required
Recessive:
________= the proportion of those carrying a genotype that express the phenotype–Phenotype can be modified by variations in penetrance and expressivity–All-or-none: either genotype = phenotype or genotype =/ phenotype)
Penetrance
_______ penetrance–Some carry the mutant allele and are phenotypically normal
Incomplete penetrance
________ = a trait is seen in all individuals carrying the mutant gene, but is expressed differently among individuals–If a gene is penetrant, it may be expressed to varying degrees–Variation in phenotype among individuals carrying a particular genotype
Variable expressivity
_____ gene defects –Affect both sexes equally
•Autosomal gene defects
_____ gene defects
–Affect males far more frequently than females
–Males cannot compensate for a defective x-linked gene with a normal counterpart of that gene on the other X chromosome
Sex-linked gene defects
______ proteins
–Mutations in genes that encode non-enzyme proteins exhibit autosomal dominant inheritance
–Structural proteins •e.g. collagen
–Membrane receptor proteins•e.g. LDL receptor
Non-enzyme proteins
_____ proteins
–Mutations in genes that encode enzyme proteins do not exhibit autosomal dominant inheritance
–50% enzyme loss can usually be compensated for and heterozygotes are usually normal
Enzyme proteins
Examples of \_\_\_\_\_\_\_\_ Diseases •Neurofibromatosis (von Recklinghausen’s disease of skin) •Marfan syndrome •Ehlers-Danlos syndromes •Nevoid basal cell carcinoma syndrome •Dentinogenesis imperfecta •Amelogenesis imperfecta (some forms)
Autosomal Dominant
- Von Recklinghausen’s disease of skin
- Autosomal dominant
- Cutaneous neurofibromas
- Café-au-lait pigmentation
- Malignant transformation
Neurofibromatosis
–NF1 gene (neurofibromin) on chromosome 17q11.2
–Cutaneous neurofibromas
–Cutaneous café au lait macules
–Lisch nodules of iris
Neurofibromatosis Type I (von Recklinghausen Disease of skin)
•Autosomal dominant inheritance
•Structural protein defect–mutation in genes that code for fibrillindefect in elastic fibers
•Involves skeleton, eyes and cardiovascular system
•Marfanoid habitus: characteristic body build
–Unusually tall with exceptionally long extremities
–Long, tapering fingers and toes
•Arachnodactly: spider-like digits
Marfan syndrome
_____ forms the Scaffolding Network of Elastic Fibers
Fibrillin
- Ectopia lentis–lens displacement with impaired vision -suspensory ligaments of lens of eye
- Mitral valve prolapse–myxomatous degeneration of the mitral valve
- Cystic medionecrosis of aorta–dilation
- Aortic valve incompetence
- Aortic dissection–common cause of death
Marfan Syndrome
- A group of inherited diseases –AD, AR, XR
- Defects in collagen synthesis and structure
- Skin, ligaments, joints•Hyperextensible skin
- Hypermobile joints
- Bleeding into the skin (ecchymoses)
- Poor wound healing
Ehlers-Danlos Syndromes
- Two copies of the allele are required for the trait to be expressed
- Carriers do not express the disease
- Skips generations
- Males and females are equally affected
- If both parents carry one copy of the recessive allele, one in four offspring, on average, will express the trait (25%)
- Frequently involves enzyme proteins
Autosomal Recessive Inheritance
Can autosomal dominant or autosomal recessive skip generations?
AR
Examples of _____ diseases
•Phenylketonuria (PKU)
•Cystic fibrosis (mucoviscidosis)
•Sickle cell anemia
Autosomal Recessive
- It is an example of an “invisible” biochemical lesion
- An autosomal recessive disorder of phenylalanine metabolism –a developmental disease
- Caused by a mutation in the enzyme that converts phenylalanine to tyrosine (phenylalanine hydroxylase)
- Phenylalanine is toxic to developing brain and causes profound, irreversible mental retardation (cognitive disorder)
Phenylketonuria
All sex-linked diseases are ____-linked
X-linked
_____ inheritance:
•Mutant genes are on the X chromosome
•Females must inherit two mutated copies to be affected
•All males who inherit the mutation will be affected (only one X chromosome)
•Transmitted by heterozygous females to their sons who manifest the disease
•Female carriers are usually protected because of random inactivation of one X chromosome (Lyonization)
•All or none in male
•Mild or non-existent in female
X-linked inheritance
Examples of _____ diseases:
•Classic hemophilia (blood clotting factor VIII deficiency)
•Bruton X-linked agammaglobulinemia (XLA)
•Duchenne muscular dystrophy
•X-linked hypophosphatemia –hypophosphatemic vitamin D-resistant rickets
•Ectodermal dysplasia
X-linked diseases
•Blood clotting factor VIII gene is on the X chromosome
•Heterozygous female phenotypically normal. Protected by presence of one normal gene
–Makes 50% factor VIII
–Laboratory abnormality
•Male son hemizygous for mutated gene on X chromosome
–Makes 0% factor VIII -has hemophilia
Classic hemophilia
•Defect in humoral immunity •Failure of B cell maturation to plasma cells No plasma cells No antibodies No germinal centers in lymphoid tissue Recurrent bacterial infections •X-linked inheritance–Affects only males •Lyonization protects females who are carriers
Bruton X-linked Agammaglobulinemia
- Not a single disorder, but a group of syndromes all deriving from abnormalities of the ectodermal structures
- Inherited, mostly X-Linked
- Sparse, fine hair
- Oligodontia
- Reduced number of sweat glands
- Nail abnormalities
Ectodermal Dysplasia
•X-linked: males are affected
•Clinical signs of rickets
•Unresponsive to Vitamin D
•Renal tubular problem:
–Can’t resorb phosphate, which is excreted in the urine
•Hypophosphatemia: low serum phosphate
•Long pulp horns extending to incisal edge of teeth
•Pulpal disease: Periapical pathosis of deciduous teeth
X-Linked Hypophosphatemia Hypophosphatemic Vitamin D Resistant Rickets
