Genetic Disorders

1. Sickle Cell
2. Marfan Syndrome
   1. The protein that plays a role in Marfan syndrome is called fibrillin-1. Marfan syndrome is caused by a defect (or mutation) in the gene that tells the body how to make fibrillin-1.
      1. TGF-β

1. Trisomy 21 (Down Syndrome)
   1. Most common, best known Chromosome know disease
   2. Most Common cause of moderate mental retardation
   3. Congenital heart disease
   4. Celiac Disease
   5. 5-fold increase in the risk of leukemia (GATA1 mutations) on the X chromosome
   6. Dementia-similar to Alzheimer disease (bAPP gene on chr21)
   7. 47,XX or XY,+21 = 95%
2. Trisomy 18 (Edwards Syndrome)
   1. wont make it after a year old, Usually a spontaneous abortion
3. Trisomy 13 (Patau Syndrome)
   1. wont make it after a year old, Usually a spontaneous abortion

1. Most common defects in liveborn infants XXY, XXX, and XYY, these are rare in spontaneous abortions
2. Turner Syndrome
   1. Most common in chromosome abnormality in spontaneous abortions
   2. MOST COMMON Monosomy for 45 X (Female)
   3. Coarctation of the Aorta (Narrowing of the Aorta)
   4. Webbed Neck
3. Klinefelter Syndrome
   1. Male with an extra X Chromosome
   2. Gynecomastia Excess development of mammary grlands SOME but not all
   3. Infertility
   4. 47,XXY (Male)

1. Chromosome #17
2. Common Autosomal Dominant disease
3. half the cases are new SPONTANEOUS rather than an inherited mutation - functions as a tumor suppressor gene
4. Pleiotropic phenotype that predisposes to benign and malignant tumors of the nervous system
5. Cafe au lait spots, Six or more spots
6. Nonmalignant peripheral nerve tumors

1. - Cystic Fibrosis 1 child in 2,000
   1. Chromosome #7
2. Tay-Sachs disease
   1. Jews in the North America
   2. Neurological disorder that develops at 6 months
   3. Lysosomal storage disorder
   4. Inability to metabolize GM2 gangliosides
3. Occurs only in Homozygotes or Compound Heterozygotes -- NEEDS 2 MUTANT ALLELES

1. Familial hypercholesterolemia (FH)
   1. Populations of European and Japanese descent
   2. Mutations in the low-density lipoprotein (LDL) receptor
   3. premature coronary artery disease (CAD)
   4. It's rare homozygous patients, but much more severe

1. Only affect males
2. phenotype only expressed in females that are Homozygous
3. Hemophilia A
   1. lack of blood clotting factor VIII
4. X-Linked = Mental retardation
5. Daughters sons HAVE A 50% chance of the mutant X
6. Daughters ALL carriers

1. Rett syndrome
   1. MECP2, a DNA-binding protein known as methyl-CpG-binding protein 2
   2. Only females, Insidious
   3. severe brain disorder that affects girls. It's usually discovered in the first two years of life

Annotations:

• A blood disorder (such as sickle-cell anemia) caused by a genetically determined change in the molecular structure of hemoglobin

1. a-Thalassemias
   1. Chromosome #16
   2. Deletions
   3. Two identical alleles
   4. Results in mild anemia and microcytosis
2. b-Thalassemias
   1. Chromosome #11
   2. Point Mutations
   3. Simple b-Thalassemia
      1. Accounts for the great majority of patients
      2. decrease in the abundance of b-globin mRNA
      3. mRNAs-have premature stop codons due to single nucleotide substitution (Gln39Stop)
      4. β+ thalassemia
         1. Polyadenylation defect (Bad Substitution AAUAAA to AACAAA)
         2. Capping defect (patient had A to C transversion)
   4. Anemia
3. Hemoglobin Kempsey
   1. - Point Mutation - Higher O2 Affinity
4. Sickle cell disease Hb-S
   1. mutation due to amino acid substitution hemoglobin
      1. Normal GAG to GTG Sickle
      2. Beta6 GLU --> VAL Sickle ---> Hb-S
   2. First two years of life present with anemia, failure to thrive, splenomegaly, repeated infections, and dactylitis
5. ARE the most common SINGLE GENE diseases in humans causes substantial morbidity
6. Complex Thalassemias
   1. remove the b-globin gene plus one or more other genes or the LCR = 19 KB
7. HPFH
   1. Deletions with in b-Globin do not cause Thalassmia but result in the phenotype termed the hereditary persistence of fetal hemoglobin (HPFH)
   2. benign condition
   3. Hb F (a2g2) compensates for the absence of Hb A

1. Deletion of about 26 genes long arm (q) of chromosome 7
   1. One of the deleted genes is elastin
      1. Elfin facial appearance
      2. Unusually cheerful, ease with strangers
      3. Supravalvular aortic stenosis