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