autosomal disorders

• Achondroplasia

  • Short limbs relative to trunk (DWARFISM), prominent forehead, low nasal root, redundant skin folds on arms and legs
  • prevents the changing of cartilage to bone
  • limited range of motion at the elbows, large head size (macrocephaly),and small fingers.
• GENE DEFECT: Fibroblast growth factor receptor 3 (FGR3)

  o makes a protein that is involved in cell division, cell maturation, formation of new blood vessels, wound healing, and bone growth, development, and

  maintenance.

  Treatment : growth hormone

  surgery aimed to correct the spine, or bone problems, and reduce the pressure inside the brain in cases of hydrocephaly.
• Hypercholesterolemia

  Clinical Feature: Impaired uptake of LDL, elevated levels of LDL cholesterol,

  cardiovascular disease and stroke. Symptoms more severe in homozygous individuals
• Gene Defect: defect on chromosome 19 and a mutation of LDL receptor

  o makes the body unable to remove low density lipoprotein (LDL, or bad

  cholesterol) from the blood or narrowing of the arteries from ATHEROSCLEROSIS at an early age
• Holoproencephaly

  • Clinical Feature: Malformation of the brain (no or reduced evidence of an interhemispheric fissure), dysmorphic facial features, mental retardation
• • GENE DEFECT: Sonic Hedgehog gene
  • Defect in Sonic Hedgehog gene may causes improper separation of the left and right brain and facial dysmorphia.
  • SONIC HEDGEHOG GENE: provides instructions for making a protein called Sonic Hedgehog protein.
  • SONIC HEDGEHOG PROTEIN: a chemical signal that is essential for embryonic development.
  • plays a role in cell growth, cell specialization, and the normal shaping (patterning) of the body.
• Huntington Disease (Huntington Chorea)

  • Clinical Feature: Disorder is characterized by progressive motor, cognitive and psychiatric abnormalities.
  • Chorea – nonrepetitive involuntary jerks – is observed in 90% of patients
  • causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition).
• • GENE DEFECT: Mutation in HTT GENE
  • HTT GENE: provides instructions for making a protein called huntingtin
  • HUNTINGTIN: play an important role in nerve cells (neurons) in the brain.
  • The HTT mutation that causes Huntington disease involves a DNA segment known as a CAG TRINUCLEOTIDE REPEAT. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row.
• Marfan Syndrome

  • Clinical Feature: Abnormalities of the skeleton (disproportionate tall stature, scoliosis), heart (mitral valve prolapse, aortic dilatation, dissection of the ascending aorta), pulmonary system, skin (excessive elasticity), and joints (hypermobility).
  • A frequent cause of death is congestive heart failure.
  • affects the connective tissue in many parts of the body.
• • GENE DEFECTS: Mutations in the Fibrillin-1 (FBN1) gene
  • Fibrillin-1 gene (FBN1) gene: provides instructions for making a protein called fibrillin-1
• Myotonic Dystrophy

  • Clinical Feature: Disorder shows anticipation. Muscle weakness, cardiac arrhythmias, cataracts and testicular atrophy in males. Children born with congenital form have a characteristic open triangle-shaped mouth
  • most common form of muscular dystrophy that begins in adulthood, usually in a person’s 20s or 30s.
• • GENE DEFECT: myotonic dystrophy protein kinase (DMPK) gene ) – CTG repeat
  • expansion in 3’ untranslated region of the gene
  • DMPK GENE: provides instructions for making a protein called myotonic dystrophy protein kinase
  • DMPK PROTEIN: appears to play an important role in muscle, heart, and brain cells.
• Neurofibromatosis I (von Recklinghausen's disease)

  • Clinical Feature: The disorder is characterized by numerous benign tumors (neurofibromas) of the peripheral nervous system, but a minority of patients also show increased incidence of malignancy (neurofibrosarcoma, astrocytoma, Schwann cell cancers and childhood CML – chronic myelogenous leukemia)
  • Areas of abnormal skin pigmentation typically include pale tan or light brown discolorations (cafe-au-lait spots), usually under the arms (axillary region) or in the groin (inguinal region).
• • Gene defect: Microdeletion at 17q11.2 involving the NF1 gene
  • NF1 gene: produces a protein called neurofibromin that helps regulate cell growth.
  • The mutated gene causes a loss of neurofibromin, which allows cells to grow

  uncontrolled.
• Osteogenesis Imperfecta

  • Clinical Feature: Null mutations produce a milder form of the disease.
  • Missense mutations that act in a dominant negative manner are often perinatal lethal.
  • Thedisorders are associated with deformed, under mineralized bones that are subject to frequent fracture.
  • causes increased bone fractures and collagen defects.
• GENE DEFECT: Either of the genes encoding the α1 or α2 chains of type I collagen

  • genes provide instructions for making proteins that are used to assemble type I collagen
  • TYPE 1 COLLAGEN: most abundant protein in bone, skin, and other connective tissue
• Polycystic Kidney Disease

  • Clinical Feature: Heterozygous individuals are predisposed to polycystic kidney disease because they are likely to lose the second good copy of the gene during their lifetime.
  • Multiple renal cysts, blood in urine, end-stage renal disease and kidney failure.
• Gene defect


  Mutations in either polycystin-1 (PKD1) or polycystin-2 (PKD2) and PKHD1 gene
• PKD1 gene


  Provides instructions for making a protein called polycystin-1
• Polycystin-1


  • Most active in kidney cells before birth
  • Much less of the protein is made in normal adult kidneys
• PKD2 gene


  Provides instructions for making a protein called polycystin-2
• Polycystin-2


  • Found in the kidneys before birth and in many adult tissues
• PKHD1 gene


  Provides instructions for making a protein called fibrocystin (sometimes known as polyductin)
• Fibrocystin


  • Present in fetal and adult kidney cells
  • Also present at low levels in the liver and pancreas
• Cystic Fibrosis

  • Clinical Feature: Pancreatic insufficiency due to fibrotic lesions, obstruction of lungs due to thick mucus, lung infections (Staph, aureus, Pseud. aeruginosa
• • Gene defect: Cystic fibrosis transmembrane regulator (CFTR) – impaired chloride ion channel function
• Gaucher’s Disease (Lysosomal storage disease)

  characterized by splenomegaly, hepatomegaly, and bone marrow infiltration.

  Neurological symptoms are not common

  do not make enough glucocerbrosidase.

  • glucocerebroside cannot be adequately degraded
• • Gene defect: Β-Glucosidase

  cause very low levels of glucocerebrosidase
• Hemochromatosis

  • Clinical Feature: Enhanced absorption of dietary iron with accumulation of abnormal, pigmented, iron-protein aggregates (hemosiderin) in visceral organs.
  • Cirrhosis, cardiomyopathy, diabetes, skin pigmentation, and arthritis.
• • Gene defect: HFE gene on the short arm of chromosome 6 (C282Y mutation)

  one mutation leads to the substitution of amino acid (Cysteine becomes tyrosine)
• Phenylketonuria

  • Clinical Feature: Mental retardation, if untreated, possibly due to inhibition of myelination and disruption of neurotransmitter synthesis. Detectable by newborn screening and treatable
• • Gene defect: Usually due to a mutation in Phenylananine hydroxylase (PAH) gene
• Tay-Sachs Disease

  • Clinical Feature:Hypotonia, spasticity, seizures, blindness, death by age 2. An early indication is a cherry red spot on the retina.
  • Gene defect: Β-Hexosaminidase A isoenzyme (HEXA) gene
• Xeroderma pigmentosum

  • Clinical Feature:Acute photosensitivity, premature skin aging, premalignant actinic keratoses, and benign and malignant neoplasms of the skin, including basal cell carcinoma, squamous cell carcinoma, or both. 5% of patients develop melanomas. Patients also exhibit ocular problems due to UV damage and have a 10- to 20-fold increased incidence of internal neoplasms due to an inability to repair DNA damage by endogenously generated and environmental genotoxic agents.
  • Gene defect: genes involved in nucleotide excision repair (locus heterogeneity)