week 12 cyto

• 1. linked dominant disorders


  • Seen more commonly in females than in males, or in the case of some diseases, affect only females (XX)
  • A mutation would have to occur in both copies of the gene to cause the disorder
  • If 1 chromosome is affected, female is considered as CARRIER
  • Hemizygous males are so severely affected, they do not survive

  
• 1. linked dominant disorders do not show father to son transmission, and affected males (hemizygous for the mutant allele) are usually more severely affected than female heterozygotes

  
• 1. linked dominant disorders

  • Rett syndrome
  • X-linked lissencephaly and double-cortex syndrome
  • Incontinentia pigmenti type 1
• 1. linked dominant disorders are uncommon relative to other types of mendelian diseases and show an excess of affected females in a family, since women have two X chromosomes
• Danon disease


  • X-linked dominant disorder characterized by intracytoplasmic vacuoles containing autophagic material and glycogen in cardiac and skeletal muscle cells in patients with cardiomyopathy and skeletal myopathy, with or without conduction defect
  • Cardiomyopathy: weakens and enlarges the heart
  • Skeletal myopathy: occurs in most men, weakness typically occurs in the muscles of the upper arms, shoulders, neck, and upper thighs
  • Elevated level of CREATINE KINASE: enzyme found in the heart, brain, skeletal muscle, and other tissues, increased amounts are released into the blood when there is muscle damage
  • WPW syndrome, visual acuity abnormalities due to choriocapillary ocular atrophy, or mental retardation
  • Caused by mutations in the LAMP 2 gene, which provides instructions for making a protein called lysosomal associated membrane protein-2 (LAMP-2)
• Incontinentia pigmenti


  • X-linked dominant disorder that is associated with seizures and mental retardation
  • Presumed to be lethal to boys in utero because nearly 100% of cases are female
  • Affects the skin, begins with a blistering rash in infancy, followed by wart-like skin growths
  • Caused by mutations in the IKBKG gene, which is involved in the regulation of the cell's division and programmed cell death and provides instructions for producing one piece (subunit) of the IKK protein complex, which regulates the activity of nuclear factor-kappa-B, which appears to play a role in the signaling pathway that is critical for the formation of ectodermal tissues including the skin, hair, teeth, and sweat glands
• Incontinentia pigmenti: Stage 1 - Vesicular stage


  Lines of blisters are present on the trunk and extremities of the newborn that disappear in weeks or months, they may resemble herpetic vesicles, microscopic examination of the vesicular fluid demonstrates eosinophils
• Incontinentia pigmenti: Stage 2 - Verrucous stage


  Lesions develop in the patient at about 3 to 7 months of age that are brown and hyperkeratotic, resembling warts, these disappear over 1 to 2 years, thick crusts or scabs with healing and areas of increased pigmentation (darkened skin)
• Incontinentia pigmenti: Stage 3 - Pigmented stage


  Whorled, swirling (marble cake–like), macular, hyperpigmented lines develop, these may fade over time, leaving only remnant hypopigmentation in late adolescence or adulthood (which is sometimes considered a fourth stage), present at birth in 5-10% of patients but usually appears between 6 and 12 months of life, disappears at about age 20 years
• Incontinentia pigmenti: Stage 4


  Skin pallor, atrophy, and scarring, reduction of hair in the involved scarred areas, both on the limbs and scalp, most evident on lower legs
• Rett Syndrome


  Most common genetic cause of severe intellectual disability in females, disorder of the nervous system that affects language skills and hand use, loss of purposeful hand use syndrome, may be diagnosed as autism or cerebral palsy, caused by mutations in the X-linked MECP2 gene which provides instructions for making MecP2 protein (abundant in brain), the available molecular data suggest that MeCP2 is a key protein in brain and that its level and functions cannot be altered without severe consequences in both genders, RTT in principle is a reversible condition and that MeCP2-related disorders can be treated even at late stages of disease progression
• 1. linked recessive disorders


  Inherited through a genetic defect on an X chromosome, causes the phenotype to be always expressed in males, females with one copy of the mutated gene are carriers
• 1. linked recessive disorders


  • Red-green color blindness, blue-yellow color vision defects (tritan defects), also known as DALTONISM, caused by mutations in the OPN1LW, OPN1MW, and OPN1SW genes (essential roles in color vision) found in retina
• Hemophilia A


  Disorder where the blood cannot clot properly due to a deficiency of a clotting factor called Factor VIII, results in abnormally heavy bleeding that will not stop, even from a small cut, people with hemophilia A bruise easily and can have internal bleeding into their joints and muscles, the occurrence of hemophilia A (Factor VIII deficiency) is around 1 in 4500 live male births, treatment is available by infusion of Factor VIII (blood transfusion), female carriers of the gene may show some mild signs of Factor VIII deficiency, such as bruising easily or taking longer than usual to stop bleeding when cut, however not all female carriers present these symptoms, one-third of all cases are thought to be new mutations in the family (not inherited from the mother)
• 1. linked disorders


  Mutated gene that causes the disorder is located on the Y chromosome, a mutation can only be passed from father to son, difficult to detect
• 1. linked disorders


  • Deafness, Y-linked 1 (DFNY1), also known as HEARING IMPAIRMENT, duplicated region was found in the DFNY1 Y chromosome, transmitted directly from father to son (y chromosome), recognizable from their male-line inheritance