Autosomal Dominant Diseases Achondroplasia [FGF-R3] activating mutation Adult polycystic kidney disease [ADPKD] Congenital spherocytosis [Ankyrein,

Spectrin, Protein 4.1] Essential Tremor Familial Adenomatous polyposis [APC] Familial hypercholesterolemia [LDL receptor] Huntington disease [CAG repeat, Huntingtin] Hypertrophic cardiomyopathy [Beta-myosin] Kallmans syndrome [KAL-1, FGF-R] Marfan syndrome [Fibrillin1] Neurofibromatosis [Neurofibromin, Merlin] Osteogenesis Imperfecta [COL1, Abnormal Type I Collagen] Tuberous sclerosis Von Hippel Lindau disease [VHL, 3p-] Von willebrand disease [Factor VIII] PTT, BT

X LINKED RECESSIVE Brutons agammaglobulinemia [RTK, Phagocytosis defect Chronic granulomatous disease [NADPH Oxidase] Color blindness Duchene muscular dystrophy [X-linked framshift, Dystrophin] Fabrys diseases [Alpha-galactosidase A] ceramide trihexoside Fragile X syndrome [FMR-1] G6PD deficiency [Product NADPH] Hemophilia A/B Hunters disease [Iduronate sufatase] Heparan Sulfate, Dermatan Severe combined immuno deficiency [Adenosine deaminase] Testicular feminization Wiscott Aldrich syndrome [Increase IgA, increase IgE, Low IgM]

X LINKED DOMINANT Alports syndrome [Abnormal collagen type IV] Familial hypophoshatemia/vitamin D resistant rickets fragile X and diabetes insipidus

AUTOSOMAL RECESSIVE [Alpha-L- Iduronidase, Accum Heparan sulphate, dermatan sulphate] [Aryle sulphatase A, Accum Cerebroside sulphate] [Beta-Glucocereborsidase, 1q21, Accm - Glucocerebroside] [Galactocerebrosidase Accum - Galactocerebroside] [Hexosaminidase-A, Accum GM2 ganglinoside] [Sphingomyelinase, Accum - Sphingomyeline] Alkaptonuria [Homogentisate oxidase] Alpha 1 antitrypsin deficiency [Emphysema, Primary biliary cirrhosis] Ataxia telangiectesia Autosomal Recessive Diseases C/F: most (not all) AR disease are enzyme deficiency, inborn error of m Classic 21-OHase deficiency Cystic fibrosis Essential fructosuria/Hereditary fructose intolerance [Fructokinase] Exceptions of Enzyme Deficiency Friedreichs ataxia [Frataxin, Chromose-9, GAA] Galactosemia [Galactokinase] Gaucher disease Hemochromatosis Homocystinuria [Cystathionine synthese, Methionine synthese] Hurler disease Krabbes disease McArdles disease [Skeletal muscle Glycogen Phosphorylase] Metachromatic Leukodystrophy Myeloperoxidase Deficiency [prevent synthesis of HOCl Niemann pick disease Non classic 21 OHase deficiency Phenylketonuria [Phenylalanine hydroxylase] Pompes disease [Lysosomal a 1, 4 glucosidase, Acid maltase] Sickle cell disease Tay sachs disease Tyrosinemia/ Hereditary tyrosinosis [Tyrosine hydroxylase] Von Gierke disease [Glucose 6 Phosphatase] Wilson's disease Xeroderma pigmentosa [Nucleotide excision repair]

Heparan sulphate, dermatan sulphate] ebroside sulphate] Accm - Glucocerebroside] alactocerebroside] 2 ganglinoside]

mphysema, Primary biliary cirrhosis]

e enzyme deficiency, inborn error of metabolism.

uctose intolerance [Fructokinase]

omose-9, GAA]

nthese, Methionine synthese]

e Glycogen Phosphorylase]

ent synthesis of HOCl

4 glucosidase, Acid maltase]

is [Tyrosine hydroxylase]

de excision repair]

ADD ADD ADD ADD ADD ADD ADD ADD ADD ADD ADD ADD ADD ADD ADD ADD ADD ADD

Achondroplasia Dwarfism

Achondroplasia Dwarfism Achondroplasia Dwarfism Achondroplasia Dwarfism Achondroplasia Dwarfism Achondroplasia Dwarfism Achondroplasia Dwarfism New gene mutations leading to achondroplasia are associated with increasing paternal Adult Polycystic kidney ADPKD disease PKD is characterized by the presence of multiple cysts (hence, "polycystic") in both kidn Adult Polycystic kidney ADPKD disease ADPKD is a late-onset disorder characterized by progressive cyst development and bila Adult Polycystic kidney ADPKD disease Cyst formation begins in utero from any point along the nephron, although <5% of total Adult Polycystic kidney ADPKD disease Over 90% of cases are inherited as an autosomal dominant trait, with the remainder like Adult Polycystic kidney ADPKD disease Mutations in the PKD-1 gene on chromosome 16 (ADPKD-1) account for 85% of cases Congenital spherocytic anemia Congenital spherocytic anemia is a disorder of the surface layer (membrane) of red blo Hereditary spherocytosis is caused by a variety of molecular defects in the genes that c Congenital spherocytic anemia Congenital spherocytic anemia The integrating protein that is most commonly defective is ankyrin which is responsible Congenital spherocytic anemia The misshapen but otherwise healthy red blood cells are mistaken by the spleen for old Hereditary spherocytosis is an autosomal dominant or recessive trait,[3] most commonly Congenital spherocytic anemia Essential tremor ET The underlying etiology is not clear but many cases seem to be familial.[14] It has been Familial Adenomatous APC polyposis Familial [APC] adenomatous polyposis can have different inheritance patterns and different ge Familial Adenomatous APC polyposis When [APC] this condition results from mutations in the APC gene, it is inherited in an autoso Familial Adenomatous APC polyposis The incidence [APC] of malignancy in these cases approaches 100%. In most cases, an affec Familial Adenomatous APC polyposis Mutations [APC]in the MUTYH gene are inherited in an autosomal recessive pattern, which m Familial hypercholesterolemia is a genetic disorder characterized by high cholesterol le Familial hypercholesterolemia FH [LDL receptor] Many patients have mutations in the LDLR gene that encodes the LDL receptor protein Familial hypercholesterolemia FH [LDL receptor] Familial hypercholesterolemia FH Patients [LDL receptor] who have one abnormal copy (are heterozygous) of the LDLR gene may have The most common genetic defects in FH are LDLR mutations, ApoB mutations, PCSK9 Familial hypercholesterolemia FH [LDL receptor] Huntington's disease, chorea, or disorder (HD), is a progressive neurodegenerative Huntington disease HD [CAG repeat, Huntingtin] Huntington disease HD [CAG repeat, The disease Huntingtin] is caused by a dominant mutation on either of an individual's two copies of All humans have the Huntingtin gene (HTT ), which codes for the protein huntingtin (HT Huntington disease HD [CAG repeat, Huntingtin] Huntington disease HD [CAG repeat, WhenHuntingtin] the length of this repeated section reaches a certain threshold, it produces an alt Huntington disease HD [CAG repeat, The Huntington's Huntingtin] disease mutation is genetically dominant, because mutation of either Hypertrophic cardiomyopathy, is a disease of the myocardium (the muscle of the heart) Hypertrophic cardiomyopathy HCM [Beta-myosin] Hypertrophic cardiomyopathy HCM Hypertrophic [Beta-myosin] cardiomyopathy is inherited as an autosomal dominant trait and is attribute Kallmans syndrome [KAL-1,Kallmann FGF-R] syndrome is a hypogonadism (decreased functioning of the glands that produ Kallmans syndrome [KAL-1,Even FGF-R] though mutations in the KAL-1 gene on the X chromosome can cause Kallmann s Kallmans syndrome [KAL-1,Autosomal FGF-R] dominant mutations have been described with the FGFR-1 (8p12) gene, som Marfan syndrome [Fibrillin1] Marfan syndrome (also called Marfan's syndrome) is a genetic disorder of the conne Marfan syndrome [Fibrillin1] It is carried by a gene called FBN1, which encodes a connective protein called fibrillin-1 Marfan syndrome [Fibrillin1] People with Marfan's are typically tall, with long limbs and long thin fingers. The most se [12] Marfan syndrome [Fibrillin1] Marfan syndrome is caused by mutations in the FBN1 gene on chromosome 15, whi Marfan syndrome [Fibrillin1] The extracellular matrix is critical for both the structural integrity of connective tissue bu Neurofibromatosis is a genetically-inherited disorder in which the nerve tissue grows t Neurofibromatosis NF [Neurofibromin, Merlin] Neurofibromatosis NF [Neurofibromin, Neurofibromatosis Merlin] type 1 - mutation of neurofibromin chromosome 17q11.2. The diagn Neurofibromatosis NF [Neurofibromin, Neurofibromatosis Merlin] type 2 - mutation of NF2 (Merlin) in chromosome 22q12. bilateral tum Osteogenesis is a genetic bone disorder. People with OI are born with def Osteogenesis Imperfecta OI [COL1, Abnormal imperfecta Type I Collagen] Osteogenesis Imperfecta OI [COL1, As a genetic Abnormal disorder, Type I OI Collagen] is an autosomal dominant defect. Most people with OI receive Type Abnormal Type I Collagen] Osteogenesis Imperfecta OI [COL1, Type Abnormal I Osteogenesis Imperfecta OI [COL1, Type I Collagen]

Achondroplasia may be inherited as an autosomal dominant trait, which means that if a child gets the defective gene from However, most cases appear as spontaneous mutations. This means that Dwarfism is a result of autosomal dominant mutation in the fibroblast growth factor rece People with achondroplasia have one normal copy of the fibroblast growth factor recept Therefore, a person with achondroplasia has a 50% chance of passing on the gene to t

Type Abnormal II Osteogenesis Imperfecta OI [COL1, Type I Collagen] Type Abnormal III Osteogenesis Imperfecta OI [COL1, Type I Collagen] Type Abnormal IV Osteogenesis Imperfecta OI [COL1, Type I Collagen] Type Abnormal V Osteogenesis Imperfecta OI [COL1, Type I Collagen] Type Abnormal VI Osteogenesis Imperfecta OI [COL1, Type I Collagen] Type Abnormal VII Osteogenesis Imperfecta OI [COL1, Type I Collagen] Type Abnormal VIII Osteogenesis Imperfecta OI [COL1, Type I Collagen]

mal dominant mutation in the fibroblast growth factor receptor gene 3 ( FGFR3 ), which causes an abnormality of cartilage formation. FGFR3 ave one normal copy of the fibroblast growth factor receptor 3 gene and one mutant copy. Two copies of the mutant gene are invariably fatal ndroplasia has a 50% chance of passing on the gene to their offspring,

o achondroplasia are associated with increasing paternal age resence of multiple cysts (hence, "polycystic") in both kidneys. The cysts are numerous and are fluid-filled resulting in massive enlargement o er characterized by progressive cyst development and bilaterally enlarged kidneys with multiple cysts. It is a genetic disorder resulting from m from any point along the nephron, although <5% of total nephrons are thought to be involved. ed as an autosomal dominant trait, with the remainder likely representing spontaneous mutations on chromosome 16 (ADPKD-1) account for 85% of cases, whereas mutations in the PKD-2 gene on chromosome 4 (ADPKD-2) represent th a is a disorder of the surface layer (membrane) of red blood cells. It leads to red blood cells that are shaped like spheres, and premature bre used by a variety of molecular defects in the genes that code for spectrin (alpha and beta), ankyrin, [4] band 3 protein, protein 4.2,[5] and other most commonly defective is ankyrin which is responsible for incorporation and binding of spectrin, thus in its dysfunction cytoskeletal instabil healthy red blood cells are mistaken by the spleen for old or damaged red blood cells and it thus constantly breaks them down, causing a cy autosomal dominant or recessive trait,[3] most commonly (though not exclusively) found in Northern European and Japanese families, altho clear but many cases seem to be familial.[14] It has been estimated that approximately one-half of the cases are due to a genetic mutation a sis can have different inheritance patterns and different genetic causes. om mutations in the APC gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cau n these cases approaches 100%. In most cases, an affected person has one parent with the condition e are inherited in an autosomal recessive pattern, which means two copies of the gene must be altered for a person to be affected by the diso is a genetic disorder characterized by high cholesterol levels, specifically very high low-density lipoprotein (LDL, "bad cholesterol") levels, in in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from the circulation, or apolipoprotein B (ApoB), whi mal copy (are heterozygous) of the LDLR gene may have premature cardiovascular disease at the age of 30 to 40. Having two abnormal cop fects in FH are LDLR mutations, ApoB mutations, PCSK9 mutations and LDLRAP1(autosomal recessive). The related disease sitosterolem ea, or disorder (HD), is a progressive neurodegenerative genetic disorder, which affects muscle coordination and some cognitive functions, ominant mutation on either of an individual's two copies of a gene called Huntingtin, which means any child of an affected parent has a 50% r n gene (HTT ), which codes for the protein huntingtin (HTT). Part of this gene is a repeated section called a trinucleotide repeat, which varies ted section reaches a certain threshold, it produces an altered form of the protein, called mutant huntingtin protein (mHTT). ation is genetically dominant, because mutation of either of a person's HTT genes causes the disease. It is not inherited according to sex, bu is a disease of the myocardium (the muscle of the heart) in which a portion of the myocardium is hypertrophied (thickened) without any obvi is inherited as an autosomal dominant trait and is attributed to mutations in one of a number of genes that encode for one of the sarcomere gonadism (decreased functioning of the glands that produce sex hormones) caused by a deficiency of gonadotropin-releasing hormone (GnR KAL-1 gene on the X chromosome can cause Kallmann syndrome, only 1114% of patients with Kallmann syndrome have detectable KAL-1 s have been described with the FGFR-1 (8p12) gene, sometimes called the KAL-2 gene. However, about 70% of KS cases seem to be the r d Marfan's syndrome) is a genetic disorder of the connective tissue. It is sometimes inherited as a dominant trait. BN1, which encodes a connective protein called fibrillin-1. People have a pair of FBN1 genes. Because it is dominant, people who have inhe ally tall, with long limbs and long thin fingers. The most serious complications are the defects of the heart valves and aorta. It may also affec y mutations in the FBN1 gene on chromosome 15,[12] which encodes a glycoprotein called fibrillin-1, a component of the extracellular matrix. cal for both the structural integrity of connective tissue but also serves as a reservoir for growth factors. [13] Elastin fibers are found throughou tically-inherited disorder in which the nerve tissue grows tumors (i.e., neurofibromas) that may be harmless or may cause serious damage b utation of neurofibromin chromosome 17q11.2. The diagnosis of NF1 is made if any two of seven criteria are met. See Wikipedia. utation of NF2 (Merlin) in chromosome 22q12. bilateral tumors, acoustic neuromas on the vestibulocochlear nerve (the eighth cranial nerve) l a genetic bone disorder. People with OI are born with defective connective tissue, or without the ability to make it, usually because of a defic n autosomal dominant defect. Most people with OI receive it from a parent but it can be an individual (de novo or "sporadic") mutation. There Description mild

severe and usually lethal in the perinatal period considered progressive and deforming deforming, but with normal scleras shares the same clinical features of IV, but has unique histologic findings ("mesh-like") shares the same clinical features of IV, but has unique histologic findings ("fish scale") associated with cartilage associated protein associated with the protein leprecan

rtilage formation. FGFR3 normally has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is co t gene are invariably fatal before, or shortly after birth

in massive enlargement of the kidneys. The disease can also damage the liver, pancreas, and in some rare cases, the heart and brain. disorder resulting from mutations in either the PKD-1 or PKD-2 gene

4 (ADPKD-2) represent the remainder heres, and premature breakdown of red blood cells (hemolytic anemia). n, protein 4.2,[5] and other erythrocyte membrane proteins nction cytoskeletal instabilities ensue them down, causing a cycle whereby the body destroys its own blood supply (auto-hemolysis). Japanese families, although an estimated 25% of cases are due to spontaneous mutations. A patient has a 50% chance of passing the mut ue to a genetic mutation and the pattern of inheritance is most consistent with autosomal dominant transmission

d gene is sufficient to cause the disorder.

to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of on ad cholesterol") levels, in the blood and early cardiovascular disease olipoprotein B (ApoB), which is the part of LDL that binds with the receptor; mutations in other genes are rare Having two abnormal copies (being homozygous) may cause severe cardiovascular disease in childhood ated disease sitosterolemia, which has many similarities with FH and also features cholesterol accumulation in tissues, is due to ABCG5 an ome cognitive functions, typically becoming noticeable in middle age. ected parent has a 50% risk of inheriting the disease. otide repeat, which varies in length between individuals and may change length between generations

erited according to sex, but the length of the repeated section of the gene, and hence its severity, can be influenced by the sex of the affected ickened) without any obvious cause. or one of the sarcomere proteins n-releasing hormone (GnRH), which is created by the hypothalamus me have detectable KAL-1 mutations S cases seem to be the result of autosomal dominant genes, though the identity of those genes is not yet known.

ant, people who have inherited one affected FBN1 gene from either parent will have Marfan's d aorta. It may also affect the lungs, eyes, the dural sac surrounding the spinal cord, skeleton and the hard palate. of the extracellular matrix. The Fibrillin 1 protein is essential for the proper formation of the extracellular matrix including the biogenesis and m bers are found throughout the body but are particularly abundant in the aorta, ligaments and the ciliary zonules of the eye; consequently, the cause serious damage by compressing nerves and other tissues ee Wikipedia. the eighth cranial nerve) leading to hearing loss. the hallmark of NF 2 is hearing loss due to acoustic neuromas around the age of twenty sually because of a deficiency of Type-I collagen. poradic") mutation. There are eight different types of OI, Type I being the most common. Gene COL1A1, COL1A2

COL1A1, COL1A2, CRTAP COL1A1, COL1A2 COL1A1, COL1A2 unknown unknown CRTAP LEPRE1

he mutated form of the receptor is constitutively active and this leads to severely shortened bones

rare cases, the heart and brain.

as a 50% chance of passing the mutation onto his/her offspring

are not affected but are carriers of one copy of the altered gene.

ation in tissues, is due to ABCG5 and ABCG8 mutations.[

influenced by the sex of the affected parent

matrix including the biogenesis and maintenance of elastic fibers onules of the eye; consequently, these areas are among the worst affected

uromas around the age of twenty