Common Diseases to Chromosomal/genetic Defects Flashcards
(115 cards)
1
Q
AML (Acute myeloblastic leukaemia)
A
Chromosome 5: deletion >> poor prognosis
Chromosome 7: deletion >> poor prognosis
t(9: 22): Philadelphia chromosome >> poor prognosis
t(8:21) >> good prognosis
t(15:17) = (PML:RAR-alpha fushion >> APML >> good prognosis
2
Q
ALL (Acute lymphoblastic leukaemia)
A
Most common: t(12: 21) = (TEL: AML1) >> good prognosis
Chromosome 9p: deletion >> good prognosis
Trisomy 4, 10, 17 >> good prognosis
Hyperdiploidy >> good prognosis
t(9:22) [Philadelphia chromosome] >> poor prognosis
t(4:11) >> poor prognosis
3
Q
CML (Chronic myeloid leukaemia)
A
t(9:22) = Philadelphia chromosome >> Poor prognosis
(ABL) Abelson proto-oncogene: location 34 of long arm (q) of chromosome 9 >> is translocated to >> BCR (Breakpoint cluster region) gene: location 11 of long arm(q) of chromosome 22
BCR: ABL encodes for tyrosine kinase
4
Q
CLL (Chronic lymphocytic leukaemia)
A
Chromosome 13 (long arm, q) >> deletion (around 50%)
Chromosome 17 (short arm, p) >> full/part deletion (around 5-10%)
5
Q
Burkitt’s lymphoma
A
t(8: 14) =
MYC oncogene on chromosome 8 >> is translocated to >> an immunoglobulin (Ig) gene on chromosome 14
6
Q
Mantle cell lymphoma
A
t (11;14) =
Deregulation of the cyclin D1 (BCL-1) gene
7
Q
Follicular adenoma
A
t(14; 18) =
Deregulation of BCL-2 gene (anti-apoptotic gene)
8
Q
Haemophilia A, B
A
‘Flip tip inversion’ in the factor VIII gene in the X chromosome (factor IX gene for type B)
9
Q
Von Willibrand disease
A
Chromosome 12 >> tip of short arm (p): VWF gene mutation
10
Q
Hereditary Haemorrhagic Telangiectasia (HHT) type 1
A
Chromosome 9;
Gene: ENG;
Protein: Endoglin
11
Q
Hereditary Haemorrhagic Telangiectasia (HHT) type 2
A
Chromosome 12;
Gene: ACVRL1/ALK-1;
Protein: ALK-1
12
Q
Hereditary Haemorrhagic Telangiectasia (HHT) type 3
A
Chromosome 5;
Gene: RASA1
13
Q
Hereditary Haemorrhagic Telangiectasia (HHT) type 4
A
Chromosome 7
Gene: unknown
14
Q
Hereditary Haemorrhagic Telangiectasia (HHT) type 5
A
Chromosome 10:
Gene: GDF2
15
Q
Juvenile Hereditary Haemorrhagic Telangiectasia (JHHT)
A
Chromosome 18;
Gene SMAD4/ MADH4
16
Q
PRV (polycythaemia rubra vera)
A
In 95% cases, Chromosome 9(p, short arm): JAK2 (V617F) mutation
17
Q
Essential thrombocythaemia
A
In 50% cases, Chromosome 9(p, short arm): JAK2 (V617F) mutation
18
Q
Myelofibrosis
A
In 50% cases, Chromosome 9(p, short arm): JAK2 (V617F) mutation
19
Q
Activated protein C resistance (Factor V leiden disease)
A
Chromosome 1: FVL gene mutation (single point mutation)
20
Q
Antithrombin III deficiency
A
Chromosome 1 (q, long arm) ; Gene: AT3 gene (AKA SERPINC gene)
21
Q
Protein C deficiency
A
Chromosome 2 (q. long arm)
Gene: PROC gene mutation
22
Q
Myeloproliferative HES (Hypereosinophilic syndrome) or Eosinophilic leukaemia
A
FIP1L1-PDFRA genotype
23
Q
Haemochromatosis
A
Chromosome: 6
Gene: C282Y HFE mutation
Also, H63D
24
Q
G6PD deficiency
A
Chromosome X
Gene: G6PD
25
**Hereditary spherocytosis**
For Northern European:
* **Chromosome 1: Gene SPTA1: Encodes: Spectrin- (alpha)**
* **Chromosome 8: Gene ANK1: Encodes: Ankyrin**
Less common:
* **Actin**
* **Protein 4.2 (Japanese)**
26
**Sickle cell disease/anaemia**
**Chromosome: 11 (p, short arm) location 6**
**Gene: HBB \>\> encodes beta-globin chain**
27
**Alpha thalassemia**
**Chromosome 16**
**Gene: HBA1 & HBA2**
So, Each chromosome has 2 gene \>\> 2 + 2 \>\> 4 gene in chromosome pair \>\> encodes alpha-globin chains/alpha subunits
28
**Beta thalassemia**
**Chromosome: 11**
**Gene: HBB**
So, Each chromosome has 1 gene \>\> 1 + 1 \>\> 2 genes in chromosome pair \>\> encodes beta-globin chains/beta subunits
29
**Von Hippel Lindau syndrome**
**Chromosome 3 (short arm, p)**
**Gene: VHL**
30
**Friedreich's ataxia**
**Chromosome 9**
**Gene: FXN (X25)**
**Protein: Frataxin**
31
**Tuberous Sclerosis (TS)**
**Chromosome 9; Gene: TSC1**
**Chromosome 16: Gene: TSC2**
32
**Neurofibromatosis**
**Type 1: Chromosome 17: Gene: NF1**
**Type 2: Chromosome 22: Gene: NF2**
(Recall, Neurofibromatosis has 17 characters, so NF1 has 17 no chromosome; NF2 has all 2)
33
**Ataxia telangiectasia**
**Chromosome 11**
**Gene: ATM gene**
**Encodes for: DNA repair enzymes**
34
**Alzheimer's disease**
**Only 5% is inherited as autosomal dominant**
**Chromosome 1: Gene: PSEN2; encodes: Presenilin 2**
**Chromosome 14; Gene: PSEN1; encodes: Presenilin 1**
**Chromosome 17: Gene: MAPT; encodes tau protein**
**Chromosome 19; Gene: APOE e4 (Apoprotein allele e4); encodes cholesterol transport protein**
**Chromosome 21: Gene: APP: encodes: Amyloid precursor protein**
35
**Huntington's disease**
**Chromosome 4**
**Gene: HTT (Huntingtin) (= IT15: Interesting type 15) gene**
**Triplet repeats: CAG**
(Recall, CAGe has 4 letters)
36
**Wilson's disease**
**Chromosome: 13**
**Gene: ATP7B**
**Encodes for: Copper-transporting ATPase 2**
37
**Myotonic dystrophy (Dystrophia myotonica)**
**Type 1: Chromosome: 19; Gene: DMPK; triplet repeat: CTG**
**Type 2: Chromosome 3: Gene: ZNF9, repeat expansion (4base pair sequence CCTG)**
**DMPK encodes for Dystrophia myotonica protein kinase**
**ZNF9 encodes for Zinc finger protein 9**
38
**Pendred's syndrome**
**Chromosome 7**
## Footnote
**Gene: PDS** gene (formerly called), **SLC26A4** (now called)
39
**Pseudohypoparathyroidism**
**Chromosome: 20**
**Gene: GNAS**
**Encodes for: Gs-alpha (alpha subunit of stimulatory G protein)**
40
**Pseudopseudohypoparathyroidism**
**Chromosome: 20**
**Gene: GNAS**
**Encodes for: Gs-alpha (alpha subunit of stimulatory G protein)**
(Same as pseudohypoparathyroidism)
41
**Nephrogenic diabetes insipidus**
**For X-linked recessive (mainly): Chromosome X; Gene: AVPR 2; Encodes for: Arginin-vasopressin receptor-2**
**For Autosomal recessive/dominant: Chromosome 12; Gene AQP2; Encodes for Aquaporin-2**
42
**Type 1 Diabetes mellitus**
**Polygenic**
**(Antibody to Glutamate Acid Decarboxylase: GAD)**
43
**MODY type 1**
**Chromosome 20**
**Gene: HNF-4 alpha (hepatocyte nuclear factor 4 alpha)**
**Encodes: hepatocyte nuclear factor 4 (a transcription factor)**
44
**MODY type 2**
**Chromosome 7**
**Gene: GCK gene (Glucokinase gene)**
**Encodes: Glucokinase**
45
**MODY type 3**
**Chromosome 12**
**Gene: HNF-1 alpha**
**Encodes for: Hepatocyte nuclear factor 1 (A transcription factor)**
(60% cases of MODY is MODY 3, 20% is MODY 2, \<10% is MODY 1)
46
**Liddle's syndrome**
**Chromosome 16**
**Gene: SCCNN 1A, 1B, 1G**
**Encodes for: ENaC (Epithelial Na channel)**
47
**Gitelman's syndrome**
(Mostly)
## Footnote
**Chromosome: 16**
**Gene: SLC12A3**
**Encodes for: Thiazide-sensitive sodium-chloride co-transporter**
48
**Familial Hyper-chylomicronaemia**
**(Type I dyslipidaemia/hyperlipoproteinaemia/hyperlipidaemia)**
**Chromosome 8**
**Gene: LPL**
49
**Familial hypercholesterolaemia**
**(Type IIA dyslipidaemia/hyperlipidaemia/hyperlipoproteinaemia)**
**Chromosome 19: Gene: LDLR (90% cases)**
**Chromosome 1: Gene: APOB**
**LDLR encodes LDL receptor protein** (which normally removes LDL from circulation)
**APOB encodes for Apolipoprotein B** (part of LDL) that binds to receptor
**(some more genetic mutations are involved but rare)**
50
**Familial combined hyperlipidaemia/hyperapobetalipoproteinaemia**
**(Type IIB Dyslipidaemia/Hyperlipoprotaeinemia/hyperlipidaemia)**
**Chromosome 19; Gene: ApoE**
**Chromosome 8; Gene: LPL & many others**
51
**Remnant hyperlipidaemia/Dysbetalipoproteinemia/Broad Beta disease**
**(Type III dyslipidaemia/hyperlipidaemia/hyperlipoproteinaemia)**
**Chromosome: 19**
**Gene: APOE-2**
**Encodes: Apo-lipoprotein E**
52
**Primary familial hypertriglyceridaemia**
**(Type IV dyslipidaemia/hyperlipidaemia/hyperlipoproteinaemia)**
**Polygenic**
**Chromosome 11; Gene: ApoA5** & many more
53
**Familial mixed hyperlipidaemia**
**(Type V dyslipidaemia/hyperlipoproteinaemia/hyperlipidaemia)**
**Chromosome 11**
**Gene: APOA5**
54
**Autoimmune polyendocrinopathy syndrome (APS)**
**Type 1: (AKA MENDAC)**
**Chromosome 21**
**Gene: AIRE1**
**Type 2: Polygenic**
(Type 1 is autosomal recessive, Type 2 is polygenic)
55
**MEN type 1 (= Wermer syndrome)**
| (Multiple endocrine neoplasia type 1)
**Chromosome 11**
**Gene: MEN1** **gene (a tumour supressor gene)**
56
**MEN type IIa (= Sipple syndrome)**
| (Multiple Endocrine Neoplasia type 2a)
**Chromosome: 10**
**Gene: RET oncogene**
57
**MEN type IIb**
| (Multiple Endocrine Neoplasia type 2b)
**Chromosome: 10**
**Gene: RET oncogene**
58
**Androgen Insensitivity Syndrome (AIS)**
**Chromosome X**
**Gene: AR**
**Encodes for: Androgen receptor**
(It has male genotype 46XY, but female phenotype; due resistance to androgen receptor)
(previously called testicular faminisation syndrome)
59
**Familial glucocorticoid remediable aldosteronism (GRA) (= Familial hyperaldosteronism type 1)**
**Chromosome 8**
**Gene: CYP11B1 & CYP11B2**
(unequal crossing over between these 2 genes result in chimeric gene)
60
**Papillary thyroid carcinoma**
**Chromosome 1**
**Gene: Trk**
**Encodes for: Tyrosine kinase receptor**
(Activation of tyrosine kinase receptor has a role in papillary thyroid carcinoma)
61
**CAH (Congenital adrenal hyperplasia)**
**Chromosome 6**
**Gene: CYP21A2**
62
**Carney complex**
**Chromosome 17**
**Gene: PRKAR1 gene**
**Encodes for: protein kinase**
63
**Peutz-Jeghers syndrome**
**Chromosome 19**
**Gene: STK11 (**also called **LKB1)**
**Encodes: Serine threonine kinase**
64
**Sporadic colon cancer**
**\>50% shows allelic loss APC gene on chromosome 5**
**Others:**
**Activation/mutation of K-ras oncogene on chromosome 12**
**Deletion of P53 on chromosome 17**
**Deletion of DCC gene on chromosome 18**
(APC encodes Adenomatour polyposis coli protein has tumour supressor properties
K-ras= oncogene encodes K-ras protein, involed in cell signalling, converts GTP to GDP
P53 is a tumour supressor gene
DCC = Deleted in colorectal carcinoma)
65
**HNPCC (Hereditary non-polyposis colorectal carcinoma)**
**More than 7 gene mutations are identified**
**The most common are:**
**hMLH1 gene on chromosome 3 (= MLH1)**
**hMSH2 gene on chromosome 2 (= MSH2)**
**hMSH6 gene on chromosome 2 (= MSH6)**
**they encode DNS mismatch repair proteins**
66
**FAP (Familial Adenomatous Polyposis)**
**Chromosome 5**
**Gene: APC mutation**
(Adenomatous polyposis gene is a tumour supressor gene)
67
**ZES (Zollinger Ellison syndrome)**
**30% is part of MEN type 1**
**So, in 30% cases,**
**Chromosome 11**
**Gene: MEN1 gene (a tumour supressor gene)**
68
**Carcinoma of pancreas**
**The most common: K-ras oncogene on chromosome 12**
If associated with HNPCC \>\> **MLH1 gene on chromosome 3**
If associated with Peutz Jegher's syndrome \>\> **STK11 gene on chromosome 19**
If associated with dysplastic naevi/melanoma \>\> **CDKN2a gene on chromosome 19**
**Also, BRCA1, BRCA2, P53**
If insulinoma of MEN1 \>\> **MEN1 gene on chromosome 11**
69
**Cowden's syndrome**
**Chromosome 10**
**Gene PTEN**
70
**Familial Juvenile polyposis**
**Chromosome 18: Gene: SMAD4**
**Chromosome 10: Gene: BMPR1A**
71
**Wilson's disease**
**Chromosome 13**
**Gene: ATP7B**
**Encodes: Copper transporting ATPase 2**
72
**Gilbert's syndrome**
**Chromosome 2**
**Gene: UGT1A1 gene**
**Encodes: UDP glucuronyl transferase**
(so, deficiency of UDP glucuronyl transferase)
73
**Dubin Johnson syndrome**
**Chromosome: 10**
**Gene: ABCC2**
**Encodes: MRP2 (Mutlidrug resistant protein 2)**
(It is deficiency of cMOAT: canalicular multispecific organic anion transporter)
74
**Rotor syndrome**
**Chromosome 12: SLCO1B1 & SLCO1B2**
75
**Crigler Najjar syndrome**
**Chromosome 2**
**Gene: UGT1A1 gene**
**Encodes: UDP glucuronyl transferase**
76
**ADPKD (Autosomal dominant polycystic kidney disease)**
**Type 1: Chromosome 16, Gene PKD1, encodes for polycystin-1**
**Type 2: Chromosome 4, Gene PKD2, encodes for polycystine-2**
77
**ARPKD (Autosomal Recessive Polycystic Kidney Disease)**
**Chromosome 6, Gene PKHD1, Encodes fibrocystin**
78
**Alport's syndrome**
**Chromosome X**
**Gene: COL 4A5**
**Encodes: Type IV collagen**
(resulting in abnormal glomerular basement membrane - GBM)
**AR & AD: COL4A4** and **COL4A3**
79
**Fanconi anaemia (syndrome)**
**Polygenic**
80
**Renal Tubular Acidosis (RTA) type 3 (Juvenile RTA)**
**Chromosome 8**
**Gene: CA II**
**Encodes: Carbonic Anhydrase 2**
(So, carbonic anhydrase 2 deficiency)
81
**Phenylketonuria (PKU)**
**Chromosome 12**
**Gene: PAH**
**Encodes: Phenyl-alanine hydroxylase**
82
**Cystinuria**
**Chromosome 2: Gene SLC3A1**
**Chromosome 9: Gene SLC7A9**
83
**Homocystinuria**
**Chromosome 21**
**Gene CBS**
**Encodes: Crystathione Beta-synthetase**
84
**Alkaptonuria**
**Chromosome 3**
**Gene HGD**
**Encodes for: Homogentisate 1,2-dioxygenase**
(so, defect in this enzyme)
85
**Bladder cancer**
**Chromosome 17p13.1, Gene P53 \>\> high grade bladder cancer**
**Chromosome 9p15 and 9p16 mutation \>\> low grade & superficial tumours**
**(Many other factor are associated with it)**
86
**Osteogenesis imperfecta**
**Chromosome 17; Gene COL1A1**
**Chromosome 7; Gene COL1A2**
(For type 1 to type 4, common autosomal dominant types)
87
**Lesch-Nyhan syndrome**
**Chromosome X (long arm, q26-26.3)**
**Gene: HPRT1**
**Enocodes for: Hypoxanthine Phosphoribosyltransferase**
(This gene is involved in purine salvage pathway, so defect results in hyperuricemia/gout)
88
**Ankylosing spondylitis**
**Its not a genetic disorder, but in some cases, present in family member/first degree relative \>\>**
**Gene: Polygenic**
**Associated with HLA-B27; All HLA is encoded by chromosome 6**
89
**Familial Mediterranean Fever (FMF)**
| (AKA recurrent polysclerositis)
**Chromosome 16**
**Gene MEFV**
**Encodes for: protein pyrin**
(PRotein pyrin is present in leukocytes, especially neutrophils & monocytes)
90
**Congenital Long QT syndrome**
| (AKA inherited/familial)
**For most common variant LQT1**
**Chomosome 11**
**Gene KCNQ1**
(Other genotypes for other variants)
Genes coding for ion channel proteins
91
**Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)**
**polygenic**
92
**Wolf-Parkinson White (WPW) syndrome**
**Chromosome: 7**
**Gene: PRKAG2**
93
**Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)**
**Chromosome 1**
**Gene RYR2 (mainly & for AD)**
**Encodes Rynodine receptor** (present in myocardium sarcoplasmic reticulum)
(Also many other genes)
94
**Brugada syndrome**
**For the most common type ( = Brugada syndrome type 1)**
**Chromosome 3**
**Gene: SCN5a**
**Encodes for: Myocardial Na ion channel protein**
95
**HOCM (Hypertrophic Obstructive Cardiomyopathy)**
**Most important:**
**Chromosome 14: Gene: MYH7 \> Encodes: Beta-myosin heavy chain**
**Chromosome 1: Gene: TNNT2 \> Encodes: Troponin T**
**Chromosome 15: Gene: TPM1 \> Encodes: Tropomyosin 1alpha/Alpha-tropomyosin**
**Other common:**
**Chromosome 11: Gene: MYBPC3 \> Encodes: Myosin binding protein C**
**Chromosome 19: Gene: TNNI3 \> Encodes: Troponin I**
**(Others are rare)**
96
**Inherited Dilated Cardiomyopathy (DCM)**
**Chromosome 5**
**Gene: SGCD**
97
**Cystic Fibrosis**
**Chromosome 7 (long arm, q); Region: Delta F508**
**Gene: CFTR**
**Encodes: cAMP regulated chloride channel**
**Delta F508 mutation = deletion of three nucleotides coding for phenylalanine residue**
98
**Hereditary breast cancer**
**Chromosome 17; Gene BRCA 1**
**Chromosome 13, Gene BRCA 2**
**P53 & others are less common**
99
**Hereditary ovarian cancer**
**Most common: Chromosome 17; Gene BRCA 1**
**2nd common: Chromosome 13, Gene BRCA 2**
**p53 & others are less common**
100
**Porphyria: Acute intermittent porphyria (AIP)**
**Chromosome 11**
**Gene HMBS**
101
**Porphyria: Familial, Porphyria cutanea tarda (PCT)**
**Chromosome 6; Gene HFE**
**Chromosome 1; Gene: UROD**
(HFE is also a chromosome of haemochromatosis)
102
**Porphyria: Variegate porphyria**
**Chromosome 6, Gene HFE**
**Chromosome 1, Gene PPOX**
(HFE gene is also responsible for PCT & haemochromatosis)
103
**Porphyria: Congenital Erythropoietic porphyria (CEP)**
**Chromosome 10**
**Gene: UROS**
104
**Abetalipoproteinaemia**
**Chromosome 4**
**Gene: MTTP**
105
**Lawrence-Moon-Biedl syndrome**
**Chromosome 19**
**Gene: PNPLA6**
106
**Retinitis pigmentosa**
**Polygenic**
## Footnote
**30% are AR: Chromosome 3: Gene: RHO \> Encodes: rhodopsin**
**Other genes are X-linked, AR, AD**
107
**Vitamin D resistant Rickets**
**Chromosome X**
**Gene: PHEX**
**(Phosphate regulating gene with homology to endopeptidases)**
108
**Incontinentia Pigmenti (IP)**
**Chromosome X**
**Gene: NEMO**
**(NF kappa B essential modulator gene)**
109
**Periventricular nodular heteroptia**
**Chromosome X**
**Gene: FLNA**
**Encodes: Filamin A**
110
**Rett syndrome**
**Chromosome X**
**Gene; MeCP2**
**Encodes: Methyl CpG-binding protein 2**
111
**Noonan's syndrome**
**Chromosome 12**
**Gene: PTPN11** (50% and most common)
**Encodes: Protein tyrosine phosphatase non-receptor type 11**
Also:**Chromosome 15, Gene MAP2K1, Encodes mitogen-activated protein kinase kinase 1** (member of MAPK kinase pathway) & several others
112
**Hereditary motor and sensory neuropathy (Charcot- Marie- Tooth disease)**
**For AD: Chromosome 17, Gene: PMP22, Encodes: Peripheral Myelin protein 22**
**For AD, AR, X-linked; other genes (polygenic)**
113
**Achondroplasia**
**Chromosome 4**
## Footnote
**Gene: FGFR 3**
**Encodes: Fibroblast Growth Factor Receptor 3**
114
**Pseudoxanthoma elasticum**
**Chromosome 16; Gene: ABCC2, XYLT1**
**Chromosome 17: Gene: XYLT2**
115
**Galactosaemia**
**Mainly,**
**Chromosome 9**
**Gene: GALT**
**Encodes: Galactose-1-phosphate uridyl transferase**
(uridyl or uridylyl)
