Diseases link to Chromosomal Abnormalities

Chromoso Abnormality Disease

me
1 -Del(1P) -Leiomyosarcoma
-Presenillin 2 gene -Early onset Alzheimer
2 -T(2:8) of MYC gene and Kappa light chains -Burkitt lymphoma
3 -LOF mutation of 3p -vHL, Renal cell carcinoma
4 -CAG repeat in the coding region -Huntington’s disease
5 -Terminal deletion of the short arm. Del (5p) -Cri-du-chat syndrome
-Mutation in 5q (del of APC gene) -Adenomatous polyposis colorectal Cancer
6 - MHC-II in macrophages
-MCH-I – alfa domain
7 -Del of Phenylalanine at position 508 (Del(7p)) -Cystic fibrosis
-Osteogenesis imperfecta
-Ehlers-Danlos syndrome
8 -T(8:14) of MYC gene to heavy Ig chain -Burkett lymphoma
-T(8:22) of MYC gene to lambda light chains
9 -T(9:22) of ABL gene -Chronic myeloid leukemia
10
11 -Point mutation in splice site or promoter -Β-Thalassemia
-Substitution of T to A (glutamic acid to Valine). -Sickle cell disease
-Substitution of glutamic acid with Lysine -HbC Disease
-Del(11p13) -Wilms tumor
-T(11:14) Bcl-1 -Mantle zone lymphoma, MM and small “not cleaved” cell lymphoma
12
13 -Mutation in 13q (del of Rb gene) -Retinoblastoma & Osteosarcoma
-BRCA-2 Breast cancer
14 - MCH-I beta domain
-T(14:18) -Small “cleaved” cell lymphoma
-Presenillin 1 gene -Early onset Alzheimer
15 -Del(15q11-q13) in father (unipaternal disomy) -Prader-Willi syndrome (obesity, polyphagia)
-Del(15q11-q13) in mother (unimaternal disomy) -Angleman syndrome
- Miss-sense mutation in fibrillin gene(FBN-1 gene) -Marfan syndrome
-T(15:17) retinoic acid receptor -AML (acute promyelocytic leukemia)
16 -Large segment deletion of α-globin chains -α-Thalassemia
-Most common cause of fetal death -PCKD
-Tuberous sclerosis
17 -LOF mutation of NF-I gene -Neurofibromatosis-I
-BRCA-1 -Breast and ovarian cancers
-P53 -Lung, breast, colon , etc.
18 -T(18:14) of Bcl-2 -Follicular lymphoma
-Mutation in 18q
-DCC gene -Colon and gastric carcinoma
-DPC gene -Pancreatic cancer
19 -CTG trinucleotide repeats -Myoclonic dystrophy
20 -MODY
21 -Down syndrome
-T(21) -ALL, AML
22 -Del(22q11) -DiGeorge syndrome
-LOF mutation of NF-II gene (22q) -Neurofibromatosis-II
-T(22:9) ABL gene -Philadelphia chromosome
23 - FMR1 gene in the long arm of X chromosome -Fragile X syndrome

T (2:8) Burkitt lymphoma T (12:22 Clear cell sarcoma

T (2:13) rhabdomyosarcoma T (12:21 ALL (good prognosis)
T (4:11) ALL and undifferentiated leukemia T (15:17) AML
T (6:9) CML with basophilia T (18:14) Follicular lymphoma
T (8:14) Burkitt lymphoma T (22:9) Philadelphia chromosome (CML) (ALL bad prognosis)

T (8:21 AML with maturation (M2) T (X: 18 synovial sarcoma

T (8:22) Burkitt lymphoma
T (9:22) CML
T (11:14 Mantle zone lymphoma, MM and small “not
cleaved” cell lymphoma
 T (11:22) Ewing sarcoma
T (14:18) Small “cleaved” cell lymphoma

Type
Autosomal Dominant
disorders:
Autosomal Recessive
disorders:
X-Linked recessive disorders
- X-Linked Dominant
- Mitochondrial inheritance
- Trinucleotide repeats
- Imprinting
- -
Mendelian inheritance
Disease
- Marfan Syndrome
- Familial hypercholesterolemia (Type IIa)
- Huntington disease
- Acute intermittent porphyria, Porphyria cutanea tarda
- Neurofibromatosis
- Hereditary hemochromatosis
- Retinoblastoma
- Xeroderma pigmentosum
- Osteogenesis imperfecta
- vHL
- Myotonic dystrophy
- 15% od Achondroplasia
- Sickle cell disease
- Cystic fibrosis
- Phenylketonuria
- Galactosemia
- Tay-Sachs disease
- Wilsons disease
- Kartegner syndrome
- McArdle disease
- Lipid storage diseases (Tay-sacks disease, Niemann-Pick disease, Gaucher disease, Metachromatic
leukodystrophy & Hurler syndrome (MPSI))
- Xeroderma pigmentosum
- Leukocyte adhesion deficiency
- Bare lymphocyte syndrome (MCH-II deficiency)
- MHC-I deficiency
- Criggler-Najjar syndrome I&II
- Duchenne muscle dystrophy
- Lesch-Nyhan syndrome
- G6PD
- Hemophilia A & B (deletion of enhancer sequence)
- Color blindness
- Menke’s disease: ATP7A (ATP-Cu efflux protein) gene abnormality.
- Ornithine transcarboxylase deficiency
- SCIS
- Lipid storage diseases (Fabray’s disease& Hunter syndrome (MPSII)
- Adrenoleukodystrophy
- Brutun agammaglobulinemia
- Hyper-IgM syndrome
- Hypophosphatemic Rickets
- Fragile X-Syndrome
- Rett syndrome
- Leber hereditary optic neuropathy
- Mitochondrial encephalopathy, lactic acidosis & stroke like episodes “MELSA”.
- Myoclonic epilepsy with ragged red muscle fibers
- Fragile X Syndrome: CGG repeat in the 5’-untranslated region.
- Huntington’s disease: CAG repeat in the coding region.
- Myotonic dystrophy: CTG repeat in the coding region.
- Frederick ataxia: GAA repeat in intron 1
- Prader-Willi syndrome (deletion of paternal and maternal imprinting)
Angleman syndrome (deletion of maternal and paternal imprinting)

Genes involved in pathology of diseases

Disease
Li-Fraumeni syndrome
Melanoma
Coronary heart disease
HNPCC (Lynch syndrome)
Alzheimer disease
Gene Involved
LOF mutation in p53 gene (Tumor suppressor gene involved in DNA repair)
P16 (Tumor suppressor gene involved in DNA repair)
CDK-4 (Proto-oncogene)
LDL-R gene (ApoB-100 receptor gene)
hMLH1, hMSH2 (mismatch repair proteins) leads to microsatellite instability)
Familial: BAPP (β-amyloid precursor protein) and Presenillin
 Sporadic: APOE ε4 (ε2 have protective effect)
DM MODY: HNF gene, GLK
IDDM: HLA-DR3/DR4/DQ
NIDDM: multiple genes
Hereditary hemochromatosis C282Y mutation (G to A substitution in codon 282)
Neurofibromatosis LOF mutation in NF gene I(chromosome 17) II ( Chromosome22)
Von-Hipple-Lindau LOF mutation in chromosome 3 (inhibit HIF “hypoxia induced factor” due to hypoxia and limit
angiogenesis)
Menke’s disease ATP7A (ATP-Cu efflux protein) gene abnormality
Ataxia-Telangiectasia syndrome ATM gene (Activates BRCA for homologous recombination)
Sporadic parathyroid adenoma Cyclin D1 Gene inversion
Autoimmune Mutation of AIRE (Autoimmune regulator gene)
hypoparathyroidism
Familial hypoparathyroidism Mutation of GCM2 (glial cell missing-2)
MEN-II Mutation of tyrosine kinase receptor RET
Brutun Agammaglobulinemia Mutation of BtK (tyrosine kinase) gene
Wickott-Aldrich syndrome mutation of WAS gene
SCID Rag 1& Rag2 deficiency
Polycythemia Vera JAK-2 Kinase mutation
Essential thrombocythemia JAK-2 Kinase mutation
1ry pulmonary hypertension Inactivation mutation in BMPR2
Wilson disease Mutation in ATP7Bgene
Autosomal dominant PCKD APKD-1 or APKD-2
Achondroplasia Activation mutation of FGFR3  inhibition of cartilage growth
Osteoporosis Carbonic anhydrase ll mutation
Ewing sarcoma T(11:22)
Muscular dystrophy Mutation/deletion in dystrophin
Amyotrophic lateral sclerosis Zinc-Cupper superoxide dismutase (SOD1)
Pulmonary hypertension BMPR2 mutation
Spinal muscle atrophy SMN1 “survival motor neuron” gene
Albright syndrome GNAS1 gene (code for α-subunit of G-protein )
(Pseudohyperparathyroidism)
Osteogenesis imperfecta COL1A1 gene

Type Mutation Disease

GF PDGF Astrocytoma
GF-receptor erbB2, HER-2/NEU Breast cancer
RET (Neuronal GF) MEN-2 , medullary thyroid cancer
KIT (Stem cell GF) Gastrointestinal stromal tumor
Transducer proteins RAS (inactive GTPase) Melanoma, Lymphoma (Most common Oncogene)
ABL (T(22:9)) CML , and some types of ALL
Transcription factor C-MYC Burkitt Lymphoma (T(8:14))
N-MYC Neuroblastoma
Oncogene

L-MYC Squamous cell carcinoma of the lung

Cyclin Cyclin-D Mantle cell lymphoma
CDK CDK-4 Melanoma
Retinoblastoma protein RB- gene Retinoblastoma
regulators TGF-β , TGF-β receptor Activates CDKI
CDKI (CD-19) Inhibit CDK and decrease phosphorylation of RB gene
Phosphatases Removes phosphates from Rb (E7 from HPV inhibits them) Cervical CA
P53 - E7 from HPV inhibits it  cervical CA
- Li-Fraumeni syndrome
E-cadherin - Gastric & esophageal CA
APC gene - Hereditary adenomatous polyposis (Inhibit β-Catenin to inhibit
transcription)
Neurofibomin -1 Neurofibromatosis – I (By activating GTPase portion of RAS)
Tumor suppressor genes

Neurofibomin -2 Neurofibromatosis – II (By producing Merlin that binds to CD44 on cell

membrane and Actin to stabilize the cell to ECM
Wilms tumor 1 Wilms tumor (Produce mesenchymal differentiation factor) (kidney
tumor)
Seen with WAGR syndrome, Denys-Drash syndrome (WT, progressive
glomerular disease and M pseudo hermaphroditism) and Beckwith-
Wiedemann syndrome (hemihypertrophy, WT , neonatal hypoglycemia
and organomegaly)
 vHL Hemangioblastoma in cerebellum and renal cell carcinoma
Regulators of apoptosis Bcl-2 (T(18:14)) Follicular lymphoma
Abnormal DNA repair MSH-2 gene HNPCC (lynch syndrome)  microsatellite instability
Nucleotide excision repair Xeroderma pigmentosum
Homologous recombination ATM Ataxia telangiectasia (Activate BRCA)
BRCA BRCA-1 (Breast and ovarian CA in females) BRCA-2 (Breast CA in males
and females)
Other Bloom syndrome and fanconi syndrome

Disease
Down syndrome
Infection w/ encapsulated bacteria
Dermatitis herpetiformis
Selective IgA deficiency
Primary hemochromatosis
Gravis disease
Ankylosing spondylitis, Psoriasis, IBS, Reiter syndrome
MS , Goodpasture’s syndrome
SLE
IDDM
Rheumatoid arthritis
Hashimoto thyroiditis
Coeliac disease
Psoriasis
Cryoglobinemia
HBsAg
Hashimoto thyroiditis
Diffuse gastric carcinoma
Pancreatic cancer
Primary sclerosing cholangitis
Minimal change disease
FSGN`
Membranous GN
Membranoproliferative GN
Crohns disease
Tuberous sclerosis
Paget disease of bone
Gout
Pseudo gout
Dermatomyositis
Cardiac rhabdomyoma
Myasthenia gravis
Lambert Eaton syndrome
Lichen planus
Dermatitis herpetiformis
Erythema multiforme
Seborrheic keratosis
Acanthosis negricans
Rheumatoid arthritis
Pernicious anemia
Fragile X syndrome
Disease
Abetalipoproteinemia
Splenectomy
Congested spleen
Rheumatic heart disease
(myocarditis)
Chronic pericarditis
Mycosis fungoides
Burkitt lymphoma
Hairy cell leukemia
Hodgkin’s lymphoma (mixed
cellularity, lymphocyte rich and
lymphocyte depleted)
Disease Associations
Association
AML (New born) ALL (Older children >5 years) Epilepsy
Splenectomy
Coeliac disease
HLA-A3
HLA- B8
HLA- B27
HLA- DR2
HLA- DR2/3
HLA- DR3/4
HLA- DR4
HLA- DR5
HLA- DQ2/8
HLA-C
Microscopic polyangiitis
Polyarteritis nodosa
Marginal zone cell” lymphoma
Acanthosis Nigerians
Leser-Trelat sign(explosive onset of multiple seborrheic keratosis)
Trousseau sign
Ulcerative colitis
Hodgkin’s lymphoma
HIV, Heroin use
HBV, HCV, solid tumors, SLE, Drugs
Type I (HBV, HCV) Type II (C3 nephritic factor)
Calcium oxalate/phosphate stones
Renal angiomyolipoma
Osteosarcoma
Monosodium urate crystals
Calcium pyrophosphate dehydrate crystals
Gastric carcinoma
Tuberous sclerosis
Thymic hyperplasia & thymoma
SCLC
Chronic HCV infection
Celiac disease
HSV (most common), Mycoplasma, Penicillin, Autoimmune diseases
(SLE), & malignancy
Leser-Trelat sign (multiple SK) in GI cancers
Type ll DM and Gastric carcinoma
Secondary amyloidosis that leads to restrictive CMP
Gastric carcinoma
Mitral valve prolapse
Characteristic cells and lesions
Lesion Description
Acanthocytosis Spiked RBC
Howell-Jolly bodies
Gandy Gumna bodies deposition of iron & calcium
Aschoff bodies & Antischkow cells(caterpillar cells)
Soldier plaques
Pautrier micro abscess
sezary cells Lymphocytes with cribriform nucleus
Starry-sky appearance Small lymphocytes interspersed with
macrophages surrounded by clear space
Tetrate resistant acid phosphatase (TRAP)
Owl eyes (reed-Sternberg cells) CD 15 , CD30
Nodular sclerosis Hodgkin’s
lymphoma
Lymphocyte predominant
Hodgkin lymphoma
CLL/SLL
Multiple myeloma
Langerhans histeocytosis
1ry amyloidosis
2ry amyloidosis
Senile cardiac amyloidosis
Familial amyloid CMP
Type II DM
Dialysis associated amyloidosis
Medullary thyroid carcinoma
Chronic pericarditis
Papillary thyroid cancer
Meningioma
Sporadic endometrial
carcinoma
Mesothelioma
Serous ovarian cystadenoma
Vocal cord nodules
Asthma
Coal worker pneumoconiosis
Asbestosis
Sarcoidosis
SCLE
SCC of the lung
Bronchi alveolar carcinoma
Diffuse type gastric cancer
Chronic cholecystitis
Alcoholic hepatitis
Diabetic nephropathy
HPV infection
Bacterial vaginosis
Endodermal sinus tumor
Sertoli-Leydig tumor
Alzheimer disease
Picks disease
Parkinson disease
Glioblastoma multiforme
Poilocytic astrocytoma
Medulloblastoma
Dermatomyositis
Liposarcoma
Rhabdomyosarcoma
Psoriasis
Lichen planus
Pemphigus vulgaris
Tuberous sclerosis
Rabies
Lacunar cells CD30
Popcorn cells CD20
Smudge cells
Flame cells, Mott cells, Bence-Johns protein, M-
component
Birbeck granules (tennis racket granules)
AL amyloid Ig light chains
AA amyloid Serum amyloid associated protein (SAA)
Non mutated transythrin (AF Amyloid)
Mutated transthyrin
Amylin Insulin
Β2 microglobin
AE amyloid Calcitonin
Soldier’s plaques
Psammoma bodies
Orphan annie eye nucleus
Psammoma bodies Small, laminated, concentric calcific spherules
found around single necrotic cell
Psammoma bodies
Psammoma bodies
Psammoma bodies
Myxoid degeneration
Curchmann spirals Spiral shaped mucus plug
Charcot-Leyden crystals Eosinophil derived crystals
Anthracosis Carbon laden macrophages
Asbestose bodies Long golden-brown fibers with associated iron
Asteroid bodies Characteristic shape of some giant macrophages
Neuroendocrine “Kulchitsky” cells
Keratin pearls and intracellular bridges
Clara cells
Signet ring, Linitis plastica, sister marry Joseph
nodule
Rokitansky-Ashoff sinus Herniation of GB mucosa into the muscular wall
Mallory bodies Damage to the intermediate filaments within
the macrophages
Kimmestile Wilson nodules
Koilocytic cells on Pap smear Immature squamous cells with dense irregularly
stained cytoplasm and perinuclear clearing
Clue cells Squamous cells covered with rods to obscure
the normal epithelial margins
Schiller-Duval bodies Glomerular like structures
Reinke crystals
Neurotic plaques Aβ amyloid
Neurofibrillary tangles Aggregates of fibers composed of hyper
phosphorylated tau protein
Pick bodies Aggregates of tau protein
Lewy bodies Round eosinophilic inclusions of α-synuclein
Glial fibrillary acid protein (GFAP)
Glial fibrillary acid protein (GFAP)
Rosenthal fibers Thick eosinophilic processes of astrocytes
Homer-Wright rosettes
Heliotrope rash, malor rash, gottron nodules
Lipoblasts
Rhabdomyoblasts Desmin positive
Auspitz sign Bleeding when scales are picked off
Wickham Stria Reticular white lines on the oral mucosa
Nikolsky sign Thin walled bulla that ruptures easily
Tomb stone appearance on histology
Fishnet appearance on immunofluorescence
Tubers Cortical hamartoma
Ash-Leaf spots Hypo pigmented patches on the skin
Negri bodies Elongated intracytoplasmic neuronal inclusions
in the hippocampus and cerebellar cortex
 Tumor markers
Cancer Marker
Medullary thyroid cancer Calcitonin
Nasopharyngeal carcinoma Keratin positive
Neuroendocrine cells Chromogranin positive
Carcinoid syndrome Chromogranin positive, positive for neuron specific enolase
Colorectal carcinoma CEA (CA lung, pancreas, stomach , breast and colon)
Pancreatic carcinoma CA19-9
Hepatocellular carcinoma Α-fetoprotein (AFP)
Paget disease PAS positive , keratin positive, S100 negative
Melanoma cells PAS Negative , keratin Negative, S100 Positive
Epithelial ovarian carcinoma CA-125
Dysgerminoma LDH
Endodermal sinus tumor AFP
Choriocarcinoma Β-HCG
Schwannoma S100
Neuroblastoma, small cell carcinoma & gastric & pancreatic carcinoma Bombisin
Seminomas Placental Alkaline phosphatase (PLAP , CD117)
Neoplastic replicative capacity Ki-67 labeling (nuclear factor)
Astrocytoma GFAP

Antibodies
Disease Association
Anti-Centromere Antibody Scleroderma (CREST syndrome)
Anti-Basement membrane Antibody Goodpasture’s syndrome
Anti-ds-DNA Antibody (Anti-smith) SLE
Anti-Scl 70 Antibody (DNA topoisomerase) Diffuse scleroderma
Anti-histone Antibodies Drug induced lupus (Isoniazid, Procainamide, Hydralazine)
Anti- RNPs antibody ( SSA[R0], SSB[La] ) Sjogren syndrome
p-ANCA (Against MPO) Chrug-Strauss syndrome, primary sclerosing cholangitis
c-ANCA (Against Proteinase 3 protein) Wegener granulomatosis
Anti- U1 Ribonucleoprotein- antibody Mixed connective tissue disease
Anti ADAMTS13 Antibody TTP
IgG against GPllb/llla ITP
Anti-Parietal cell antibody Pernicious anemia
Anti-intrinsic factor antibody
Anti-intrinsic factor receptor antibody
Anti-Heterophil antibody (IgM against horse RBC) Infectious mononucleosis
Anti-Rh-IgG antibody Worm antibody IHA
Anti-I-IgM Antibody Cold hemagglutinin IHA
Anti-P-IgG-Antibody Cold hemolysin antibody
Anti-thyroglobulin antibody Hashimoto thyroiditis
Anti-thyroid peroxidase antibody
AMA
Anti-Mitochondrial antibody (AMA) Primary biliary cirrhosis
Rheumatoid arthritis IgM antibody against Fc portion of IgG (rheumatic factor)
Dermatomyositis , Polymyositis ANA
Anti-Jo-Antibody (Anti-histidyl-tRNA synthetase antibody)
Myasthenia gravis Anti-Ach receptor-Antibody
Lambert-Eaton syndrome Anti-calcium receptor antibody in the presynaptic neuron
Pemphigus vulgaris IgG-Antibodies against Desmoglein
Bullous pemphigoid IgG-Antibodies against hemidesmosomes (BP1810, BP Ag1, BP Ag 2 ,
Alfa-6 Integrin & Laminin 5)
Heparin induced thrombocytopenia (HIT) IgG against PF4