Genetics for the Internist - I.ppt

Genetics for the Internist - I Charles J. Macri, MD Departments of Obstetrics and Gynecology National Naval Medical Center] Bethesda Maryland Why do we have to know this? Board examination Residency examination Wardsmanship Intellectual stimulation Patient Care Your friends will ask you Resources I have chosen Mayo Internal Medicine Board Review 1996-1997 MKSAP 10 Current literature Computer databases - OMIM, NIH Genetics Overview of Genetic Concepts Basic human genetic principles context of everyday clinical practice relevance of human genome project how genes behave in families and individuals major forms of human inheritance importance of clinical laboratory ID of at risk individuals clinical laboratory techniques available management of hereditary disorders Introduction Chromosome Abnormalities Patterns of Inheritance Mendelian Non-Mendelian Mitochondrial mutations Multifactorial inheritance Presymptomatic diagnosis Prenatal diagnosis Molecular strategies Inheritance Chromosomal numerical, structural, microdeletions Single gene - CF, Sickle cell Multifactorial CHD, pyloric stenosis, Cleft lip/palate, NTDs Triplet nucleotide repeats Mitochondrial inheritance Inheritance UPD - Uniparental disomy Imprinting - Prader willi, Angleman - 15 q 21 Trinucleotide repeat sequences Fragile X, Myotonic dystrophy, Huntington Disease, SBMA Mitochondrial inheritance MELAS, LHON Leber’s hereditary optic neuopathy Hints that Genetic Cause is likely Atypical age of onset - Angina before 50 Episodic occurrences - Acute intermittent porphyria, periodic paralysis, recurrent syncope Multiple occurrences - Bilateral tumors, multiple primary tumors, multiple cafe au lait spots (NF) Seemingly unrelated conditions - presenting symptom plus MR, infertility or cong malf Some examples of Genetic Disorders in IM Familial Long QT syndrome BRCA1 - breast/ovarian CA susceptibility Neuofibromatosis 1 and 2 Alzheimer’s disease - apolipoprotein E locus Gaucher’s disease Osler-Weber-Rendu syndro