Genetics
Single Gene Disorders
- Single nucleotide polymorphism (SNP)
- Silent mutation
- Missense mutation
- Nonsense mutation
- Indel mutation
- Frameshift mutation
- Tandem repeat: microsatellite & minisatellite
Chromosomal Disorders
- Numerical mutation
- Autosomal monosomy
- Autosomal trisomy
- Sex chromosome monosomy :: Turner syndrome
- Sex chromosome trisomy :: Klinefelter syndrome
- Structural mutation
- Inversion
- Duplication
- Insertion & Deletion
- Translocation: Robertsonian & reciprocal
- Isochromosome
- Ring chromosome
Trinucleotide Repeat Expansion Disorders
| Mnemonic | Disorder | Inheritance | Gene | Product | Repeat |
|---|---|---|---|---|---|
| Hunting | Huntington disease | AD | HTT | Huntingtin | CAG |
| For | Friedreich ataxia | AR | FXN | Frataxin | GAA |
| My | Myotonic dystrophy | AD | MDPK | Protein kinase | CTG |
| Sexy | Spinobulbar muscular atrophy (SBMA) | XR | AR | Androgen receptor | CAG |
| X | Fragile X syndrome | XD | FMR1 | FMR protein | CGG |
Presentation of Fragile X Syndrome
- Long face
- Large jaw
- Everted ears
- Macroorchidism
- Autism
Microdeletion Disorders
| Disorder | Chromosome |
|---|---|
| Angelman syndrome | 15q |
| Cri-du-chat syndrome | 5p |
| DiGeorge syndrome | 22q11 |
| Prader-Willi syndrome | 15q |
| Williams syndrome | 7q |
Presentation of Cri-du-chat Syndrome
- Microcephaly
- Cardiac anomalies
- High-pitched crying
Presentation of DiGeorge Syndrome {CATCH22}
- Cardiac anomalies :: tetralogy of Fallot (TOF)
- Abnormal facies
- Thymic aplasia
- Cleft palate
- 1° Hypoparathyroidism → Hypocalcemia
- 22q11 microdeletion
Imprinting Disorders
| Disorder | Maternal | Paternal |
|---|---|---|
| Angelman syndrome | Mutation | Imprinting |
| Prader-Willi syndrome | Imprinting | Mutation |
| Pseudohypoparathyroidism (PHP) | Mutation | Imprinting |
Autosomal Trisomies
| Down Syndrome | Edwards Syndrome | Patau Syndrome | |
|---|---|---|---|
| Mnemonic | Drinking | Election | Puberty |
| Chromosome | 21 | 18 | 13 |
| PAPP-A | ↓ | ↓ | ↓ |
| hCG | ↑ | ↓ | ↓ |
| AFP | ↓ | ↓ | - |
| Estriol | ↓ | ↓ | - |
| Inhibin A | ↑ | ↓ | - |
Presentation of Autosomal Trisomies
Presentation of Turner Syndrome
- Short stature
- Webbed neck
- Shield chest
- Bicuspid aortic valve
- Coarctation of the aorta
- Cystic hygroma
- Horseshoe kidney
- Streak ovaries
- Amenorrhea
Hereditary Disorders
Autosomal Dominant (AD)
| Disease | Gene | Product |
|---|---|---|
| ADPKD | PKD1 PKD2 | Polycystin 1 Polycystin 2 |
| Acute intermittent porphyria | - | Porphobilinogen deaminase |
| Familial hypercholesterolemia | LDLR | LDL receptor |
| Huntington disease | HTT | Huntingtin |
| Marfan syndrome | FBN1 | Fibrillin |
| Multiple endocrine neoplasia (MEN) 1 | MEN1 | Tyrosine kinase |
| Multiple endocrine neoplasia (MEN) 2 | RET | Menin |
| Neurofibromatosis (NF) type 1 Neurofibromatosis (NF) type 2 | NF1 NF2 | RAS activators |
| Porphyria cutanea tarda | - | Uroporphyrinogen decarboxylase |
| Tuberous sclerosis | TSC1 TSC2 | Hamartin Tuberlin |
| Von Hippel-Lindau (VHL) disease | VHL | HIF inhibitors |
Autosomal Recessive (AR)
| Disease | Gene | Product |
|---|---|---|
| ARPKD | PKHD1 | Fibrocystin |
| Oculocutaneous albinism | TYR | Tyrosinase |
| Phenylketonuria (PKU) | PAH | Phenylalanine hydroxylase Tetrahydrobiopterin |
| Alkaptonuria (AKU) | HGD | Homogentisate oxidase |
| Homocystinuria | - | Cystathionine synthase Methionine synthase |
| Cystinuria | - | Amino acid transporter |
| Hartnup disease | - | Amino acid transporter |
| Maple syrup urine disease (MSUD) | - | Branched-chain α-ketoacid dehydrogenase |
| Cystic fibrosis (CF) | CFTR | Cl channel |
| Kartagener syndrome | - | Dynein |
| Sickle cell disease (SCD) | - | β-Globin |
| Thalassemia | - | α-Globin β-Globin |
| Hemochromatosis | HFE | Iron regulator protein |
| Wilson disease | ATP7B | Cu channel |
| Glycogen storage diseasess (GSD) | - | - |
| Lysosomal storage diseasess (LSD) | - | - |
X-linked Dominant (XD)
| Disease | Gene | Product |
|---|---|---|
| Alport syndrome | COL4 | Type 4 collagen |
| Fragile X syndrome | FMR1 | FMR protein |
| Rett syndrome | MECP2 | Methyl-CpG binding protein 2 (MeCP2) |
X-linked Recessive (XR)
| Disease | Gene | Product |
|---|---|---|
| Bruton agammaglobulinemia | BTK | Bruton tyrosine kinase |
| Duchenne muscular dystrophy (DMD) Becker muscular dystrophy (BMD) | DMD | Dystrophin |
| Fabry disease | - | α-Galactosidase |
| G6PD deficiency | G6PD | Glucose-6-phosphate dehydrogenase |
| Haemophilia A & B & C | - | Factor 8 & 9 & 11 |
| Hunter syndrome | - | Iduronate sulfatase |
| Lesch-Nyhan syndrome | HPRT1 | HGPRT |
| Menkes disease | ATP7A | Cu channel |
| Ocular albinism | - | - |
| Ornithine transcarbamylase deficiency | - | Ornithine transcarbamylase |
| Wiskott-Aldrich syndrome | WAS | WAS protein |
Presentation of McCune-Albright Syndrome
- Polyostotic fibrous dysplasia
- Cafe-au-lait spots
- Precocious puberty