Genetic Disorders, Diseases of the Immune System, Neoplasia Flashcards
Gene Defect of Marfan Syndrome
Fibrillin-1 (Chromosome 15)
Defect in Ehlers-Danlos Syndrome
Fibrillar Collagen
AD: Collagen structural genes (COL)
AS: Enzymes in collagen synthesis
Organs affected by Marfan syndrome
Skeleton
Eyes
CVS
Characterization of lens subluxation in Marfan syndrome
Outward and upward
*homocystinuria - inward and downward
Gene in Ehlers Danlos types
Classic (I/II) - COL5A1, COL5A2
Hypermobility (III) - Unknown
Vascular (IV) - COL3A1
Arthrochalasia (VIIa, VIIb) - COL1A1, COL1A2
Kyphoscoliosis (VI) - Lysyl hydroxylase
Dermatosparaxis (VIIc) - Procollagen N-peptidase
Defect in Familial Hypercholesterolemia
LDL receptor mutation (Class I-VI)
I - synthesis
II - transport
III - Binding
IV - Clustering
V - Recycling
VI - Initial targeting
What type of Genetic Disorder?
AD
AS
X-D
X-S
Huntington Disease
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Neurofibromatosis
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Myotonic dystrophy
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Tuberous Sclerosis
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Polycystic Kidney Disease
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Familial polyposis coli
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Hereditary spherocytosis
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Von Willebrand Disease
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Marfan Syndrome
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Ehlers Danlos Syndrome
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Osteogenesis imperfecta
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Achondroplasia
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Familial hypercholesterolemia
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Acute Intermittent Porphyria
AD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Cystic fibrosis
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Phenylketonuria
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Galactosemia
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Homocystinuria
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Lysosomal Storage Diseases
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
a-1 antitrypsin deficiency
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Wilson disease
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Hemochromatosis
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Glycogen storage diseases
What type of Genetic Disorder?
AD
AS
X-D
X-S
Sickle Cell Anemia
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Thalassemias
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Congenital Adrenal Hyperplasia
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Alkaptonuria
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Neurogenic muscular atrophies
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Friedrich ataxia
AS
What type of Genetic Disorder?
AD
AS
X-D
X-S
Spinal muscular atrophy
AS
Defect in Tay Sachs Disease
Hexosaminidase
Defect in Niemann-Pick Disease
Sphingomyelinase
Cherry red spot in macula w/o visceral involvement
Tay Sachs disease
Cherry red spot in macula w/ visceral involvement
Niemann-Pick Disease
Zebra bodies
Niemann-Pick Disease
Enzyme deficiency in Pompe dse
a-1,4-Glucosidase
Enzyme deficiency in Gaucher dse
Glucocerebrocidase (B-glucosidase)
Enzyme deficiency in Fabry dse
a-Galactosidase A
Enzyme deficiency in Farber disease
Ceramidase
Enzyme deficiency in Krabbe dse
B-Galactosidase (Galactosylceramidase)
Enzyme deficiency in Metachromatic leukodystrophy
Arylsulfatase A
Enzyme deficiency in Hurler Syndrome (MPS-IH)
a-L-Iduronidase
Enzyme deficiency in Hunter Syndrome (MPS-II)
Iduronate 2-sulphatase
Disorder in aromatic amino acids (phenylalanine and tyrosine)
Alkaptonuria - homogentisic acid oxidase deficiency
Dark blue to black pigmentation in connective tissue and cartilage in Alkaptonuria
Ochronosis
Most common form of hypogonadotropic hypogonadism
Kallman syndrome - failure of olfactory axons and GnRH expressing neurons to migrate from olfactory placode to brain (w/ anosmia)
X-Linked:KAL1 - Xp22.3
AD: KAL2 - FGFR1
AS: KISS1 - Kisspeptin
What type of Genetic Disorder?
AD
AS
X-D
X-S
Duchenne Muscular Dystrophy
XR
What type of Genetic Disorder?
AD
AS
X-D
X-S
Hemophilia A and B
What type of Genetic Disorder?
AD
AS
X-D
X-S
XR
What type of Genetic Disorder?
AD
AS
X-D
X-S
Chronic granulomatous disease
XR
What type of Genetic Disorder?
AD
AS
X-D
X-S
G6PD
XR
What type of Genetic Disorder?
AD
AS
X-D
X-S
Agammaglobulinemia
XR
What type of Genetic Disorder?
AD
AS
X-D
X-S
Wiskott-Aldrich syndrome
XR
What type of Genetic Disorder?
AD
AS
X-D
X-S
DI
XR
What type of Genetic Disorder?
AD
AS
X-D
X-S
Lesch-Nyhan syndrome
XR
What type of Genetic Disorder?
AD
AS
X-D
X-S
Fragile X syndrome
XR
What type of Genetic Disorder?
AD
AS
X-D
X-S
Alport syndrome
XD
What type of Genetic Disorder?
AD
AS
X-D
X-S
Vitamin D-resistant rickets
XD
Gaucher disease is a generic risk factor for
Parkinsons disease
Crumpled tissue paper appearance of cytoplasm
Gaucher cells
Arsenic
Lung, Skin cancer
Asbestos
Lung, esophagus, stomach, colon, mesothelioma
Benzene
AML
Beryllium
Lung cancer
Cadmium
Prostate ca
Chromium
Lung ca
Nickel
Lung and oropharynx ca
Radon
Lung ca (#1)
Vinyl chloride
Hepatic angiosarcoma
Estrogen
Breast and endometrial ca
Androgen
Prostate ca
Select tumor markers: hCG
Trophoblastic tumors
Non-seminomatous germ cell tumors
Select tumor markers: calcitonin
Medullary thyroid carcinoma
Select tumor markers: catecholamines and metabolites
Pheomchromocytoma
Select tumor markers: alpha-fetoprotein
Hepatocellular carcinoma
Non-seminomarous germ cell tumors of testis (Yolk sac tumors)
Select tumor markers: Carcinoembryogenic antigen (CEA)
Colorectal, pancreas, lung, stomach, heart carcinoma
Select tumor markers: immunoglobulins
Multiple myeloma, other gammopathies
Select tumor markers: PSA and PSMA
Prostate CA
Select tumor markers: CA 125
Ovarian ca
Select tumor markers: CA 19-9
Colon and pancreatic ca
Select tumor markers: CA 15-3
Breast ca
One dominant allele is
enough to produce
phenotype (heterozygous)
Autosomal dominant (AD)
AD disorder characterized by
a defect in fibrillin-1 gene
(chromosome 15)
Marfan syndrome
Most striking feature in
Marfan syndrome
Skeletal abnormalities e.g.
pectus excavatum /
carinatum, dolichocephalic,
kyphosis/scoliosis
Most life-threatening feature
in Marfan syndrome
Cardiovascular
abnormalities e.g. MVP,
aortic dissection, aortic
insufficiency
Two recessive alleles
produce phenotype
Autosomal recessive (AR)
AR disorder with a defect in
hexosaminidase A causing
accumulation of GM2
ganglioside in neurons and
retina
Tay-Sachs disease
AR disorder with
sphingomyelinase deficiency
Niemann-Pick disease
Most common lysosomal
storage disorder; (+)
crumpled tissue paper on
PAS; deficiency in glucocerebrocidase
Gaucher disease
Usually males express
phenotype; Females may
express the phenotype (due
to inactivation of one X
chromosome)
X-linked recessive (XR)
X-linked recessive blood
disorders
Hemophilia A and B, G6PD
deficiency, CGD
Example of X-linked
dominant disorders
Alport syndrome and
Vitamin D-resistant rickets
Most common chromosomal
disorder; leading cause of
mental retardation
Trisomy 21
Edward syndrome
Trisomy 18
Patau syndrome
Trisomy 13
Most common chromosomal
abnormality in Klinefelter
syndrome
47XXY (90%)
Most consistent finding in
Klinefelter syndrome
Hypogonadism
Heart abnormality associated
with Klinefelter syndrome
Mitral valve prolapse
(50%)
Single most important cause
of primary amenorrhea
Turner syndrome
Most common chromosomal
defect in Turner Syndrome
Cardiovascular
abnormalities (preductal
CoA, bicuspid aortic valve,
aortic root dilation, aortic
dissection)
2nd most common cause of
mental retardation after
Trisomy 21
Fragile X syndrome
Defect in Fragile X syndrome
CGG expansion
Most distinctive feature in
Fragile X syndrome
Macroorchidism
CAG expansion; dementia +
movement disorders
Huntington disease
Deletion in paternallyderived
chromosome 15; (+)
obesity, hyperphagia, short
stature
Prader-Willi syndrome
Deletion in maternallyderived
chromosome 15;
inappropriate laughter
“happy puppet
Angelman Syndrome
Examples of mitochondrial
disorders (maternal
inheritance)
Mitochondrial myopathy,
Encephalopathy, Lactic
Acidosis and Stroke
(MELAS), Leber Hereditary
Optic Neuropathy (LHON)
Only cell in the body that can
produce antibodies
B Lymphocytes i.e. Plasma
cells
Most important antigenpresenting
cell for initiating
T-cell responses against
protein antigens
Dendritic cells
Type of antibody that can
cross the placenta
IgG
IgE-mediated type of
hypersensitivity
Type I or Immediate
hypersensitivity
Examples of Type I
hypersensitivity
Asthma, anaphylaxis,
allergies
Antibody-mediated type of
hypersensitivity
Type II
Examples of type II
hypersensitivity
Immune hemolytic anemia,
Rheumatic fever,
Myasthenia gravis,
Goodpasture syndrome,
Graves disease
Immune complex-mediated
type of hypersensitivity
Type III
Most common sites of
immune complex deposition
Kidneys, joints
Examples of type III
hypersensitivity
SLE, PSGN, Polyarteritis
nodosa, Reactive arthritis
T cell-mediated or delayed
type of hypersensitivity
Type IV
Examples of type IV
hypersensitivity
RA, T1DM, TST, IBD,
Psoriasis, Multiple
sclerosis, contact
sensitivity
HLA type associated in
seronegative
spondyloarthropathies
HLA-B27
Most sensitive and best
screening test for SLE
AAnti-nuclear antibody
(ANA)
Specific test for SLE that
correlates with disease
activity
Anti-dsDNA
Autoantibody associated with
drug-induced lupus
Anti-histone
Autoantibody associated with
neonatal lupus and
congenital heart block
Anti-Ro (SS-A)/ Anti-La (SSB)
Antiphospholipid antibodies
Anticardiolipin and β2-
glycoprotein I
Autoimmune disease
directed against lacrimal and
salivary glands; (+)
xerostomia (dry mouth) &
keratoconjunctivitis sicca
(dry eyes)
Sjogren syndrome (SS)
Most important and most
common associated
autoantibodies associated
with SS
Anti-Ro (SS-A) Anti-La (SSB)
Earliest histologic finding in
SS
Periductal and
perivascular lymphocytic
infiltration
Most common associated
disease with SS
Rheumatoid arthritis
Patients with SS have
increased risk to develop
what type of malignancy
Lymphoma
EXcessive fibrosis throughout
the body
Systemic Sclerosis
(Scleroderma)
Type of scleroderma that has
widespread skin
involvement, rapid
progression, early visceral
involvement
Diffuse scleroderma
Autoantibody associated with
diffuse scleroderma
Anti DNA topoisomerase I
(anti-Scl 70)
Type of scleroderma with
limited skin and visceral
involvement
Limited scleroderma or
formerly known as CREST
syndrome
Clinical features of CREST
syndrome
Calcinosis, Raynaud
phenomenon,
Esophageal dysmotility,
Sclerodactyly,
Telangiectasia
Autoantibody associated with
limited scleroderma
Anti-centromere
Disease with clinical features
that overlap with those of
SLE, systemic sclerosis, and
polymyositis
Mixed Connective Tissue
Disease
Autoantibody associated with
mixed connective tissue
disease
Anti-U1-RNP
AR disease associated with
selectin/integrin
abnormalities; (+) delayed
separation of the umbilical
cord, omphalitis
Leukocyte Adhesion
Deficiency
XR disease characterized by
NADPH oxidase deficiency;
(+) susceptibility to catalasepositive
organism
Chronic Granulomatous
Disease
XR disease characterized by
failure of B cell maturation;
respiratory and GIT
infections at 6 months of age
Bruton
agammaglobulinemia
Defect in DiGeorge syndrome
Chromosome 22q11
deletion→Failure of
development of pharyngeal
pouches (thymus and
parathyroid glands)
Clinical features of DiGeorge
syndrome
CATCH22 – Cardiac
abnormalities, abnormal
facies, thymic aplasia, cleft
palate, hypocalcemia/
hypoparathyroidism
Triad of Wiskott-Aldrich
Syndrome
Thrombocytopenia (with
small platelets), Recurrent
infections, Eczema
Most serious secondary
immunodeficiency
Acquired
immunodeficiency
syndrome (AIDS)
Most abundant HIV antigen;
detected in screening tests
for HIV infection
p24
First stage of infection with
HIV; Symptoms include flulike
illness, rash, cervical
adenopathy, diarrhea,
vomiting
Acute Retroviral Syndrome
or Acute HIV Syndrome
Examples of AIDS-defining
illnesses
Opportunistic infections,
secondary neoplasms, CNS
disease
Most common fungal
infection associated with
AIDS
Candidiasis
Most common neoplasm
associated with AIDS; causes
by HHV-8
Kaposi Sarcoma
Most common type of
lymphoma in AIDS
B-cell Lymphoma
Hemodialysis-associated
amyloid protein
Aβ2m: β2- microglobulin
Amyloid protein in Alzheimer
disease
Aβ: Amyloid precursor
protein
Most common and
potentially most serious form
of organ involvement
Renal involvement
Formation of abundant
collagenous stroma in response
to parenchymal cells
Desmoplasia
Tumor containing recognizable
mature or
immature tissues belonging to
more than one germ cell layer
Teratoma
Disorganized mass composed
of cells indigenous
to the involved tissue
Hamartoma
Term applied to heterotopic
(misplaced) but
organized rest of cells (aka
heterotopia, ectopia)
Choristoma
Lack of differentiation;
Hallmark of malignancy
Anaplasia
Architectural disarray, loss of
orderly maturation, and
cytologic atypia confined within
the epithelium; “disordered
growth”
Dysplasia
Unequivocal marker of
malignancy
Metastasis
Route of dissemination
typically seen in carcinomas
Lymphatic spread
Route of dissemination
typically seen in sarcomas
Hematogenous spread
Most favored sites of
hematogenous spread
Lungs, liver
Most common cancer in males
Prostate cancer
Most common cancer in
females
Breast cancer
Most common cause of cancer
death in both males and
females
Lung cancer
Normal gene whose products
promote cellular proliferation
Proto-oncogene
Most common type of
abnormality involving protooncogenes
in human tumors
RAS
Tumor suppressor gene that
regulates G1-S checkpoint;
governor of proliferation
RB
Most frequently mutated gene
in human cancers
TP53
Cancer associated with
cholangitis or Opsithorchis
viverrini infection
Extrahepatic
cholangiocarcinoma
Cancer associated with
Hashimoto thyroiditis and
Sjogren syndrome
Marginal zone lymphoma
Asbestosis-related cancers
Mesothelioma, lung
carcinoma
Cancer associated with
Schistosoma haematobium
infection
Bladder squamous cell
carcinoma
HPV-associated cancers
Oropharyngeal, Cervical,
Vulvar, Penile
carcinomas
HTLV-1-associated cancer
Adult T cell
leukemia/lymphoma
Vinyl chloride-associated
cancer
Hepatic angiosarcoma
Cadmium-associated cancer
Prostate cancer
Benzene-associated cancer
Acute myeloid leukemia
Signs and symptoms not
referable to the anatomic
distribution of the tumor; due
to hormones or substances
elaborated by the tumor
Paraneoplastic syndrome
Most common endocrinopathy
Cushing syndrome
Most common paraneoplastic
syndrome
Hypercalcemia
Serum abnormalities observed
in tumor lysis syndrome
Hyperkalemia,
hyperphosphatemia,
hyperuricemia,
hypocalcemia
Tumor marker for medullary
thyroid carcinoma
Calcitonin
Tumor marker for
hepatocellular carcinoma, nonseminomatous
germ cell
tumors of testis
α-fetoprotein (AFP)
