Autosomal recessive diseases cystic fibrosis

Cystic fibrosis is the most common lethal autosomal-recessive disease, in which oxidative stress takes place at the airway surface [274]. This disease is characterized by chronic infection and inflammation. Enhanced free radical formation in cystic fibrosis has been shown as early as 1989 [275] and was confirmed in many following studies (see references in Ref. [274]). Contemporary studies also confirm the importance of oxidative stress in the development of cystic fibrosis. Ciabattoni et al. [276] demonstrated the enhanced in vivo lipid peroxidation and platelet activation in this disease. These authors found that urinary excretion of the products of nonenzymatic lipid peroxidation PGF2 and TXB2 was significantly higher in cystic fibrotic patients than in control subjects. It is of importance that vitamin E supplementation resulted in the reduction of the levels of these products of peroxidation. Exhaled ethane, a noninvasive marker of oxidative stress, has also been shown to increase in cystic fibrosis patients [277]. 

Cystic fibrosis (CF) is the most common potentially lethal autosomal recessive disease among Caucasians. The incidence is estimated to be approximately 1 in 2000 births (Bl). Since it is inherited as an autosomal recessive condition, screening to identify couples at risk has been suggested. However, CF screening is complicated because many mutations of the CF gene exist. Thus, the feasibility of screening a population for carriers of cystic fibrosis gene mutations is primarily dependent upon the frequency of the common mutation in that population. 

Cystic fibrosis is an autosomal recessive disease caused by mutations of the cystic fibrosis transmerobrane conductance regulator (CFTR) gene producing a dysfunctional chloride channel, normally located on the apical membrane of exocrine glands [16]. The disease manifests itself at an early age in the lung with accumulation of thick, sticky mucus and bacterial infections. These infections are followed by an inflammatory response, resulting in an Infiltration of neutrophils... 

Mucoviscidosis or cystic fibrosis (CF) is indeed one of the most common autosomal recessive diseases. It is characterized by the production of a viscous secretion in the excretory glands. Accordingly, pancreatic cystic fibrosis can be observed in the pancreatic area and cylindrical bronchiectases in the pulmonary area. The inspissation of bile and mucus leads to obstruction of the bile canaliculi and subsequently to cholestasis. The gene product is characterized as cystic fibrosis transmembrane regulator (CFTR). (252) The gene defect, which is located on chromosome 7, causes a disorder of the intracellular transport of chloride ions (probably also of chloride ion secretion) and thus triggers the occurrence of CF. The incidence of mucoviscidosis is about 1 2,000-4,500. 

Cystic fibrosis (CF) is the most common severe autosomal recessive disease, with an estimated gene frequency in Western Europe and the United States of between 1 25 and 1 35 and a disease incidence of about 1 in 2500 to 1 in 3200. The pathogenesis and diagnosis of CF are described in Chapter 40. Pancreatic insufficiency is present at birth in 65% of infants with CF, and a further 15% develop it during infancy and early childhood. The 20% who do not develop pancreatic insufficiency have a better prognosis and develop fewer complications. 

Cystic fibrosis is the most common lethal autosomal recessive disease affecting the Caucasian population. It has a frequency of approximately 1 in 2500 and a carrier frequency of approximately 1 in 25. The protein affected is the cystic fibrosis transmembrane conductance regulator (CFTR), which is a chloride ion channel. There are over 1000 mutations that have been discovered in the CFTR gene and over 80 percent of these mutations lead to disease. The mutations lead to (1) defective or decreased protein production, (2) defective processing of the protein, (3) protein that is defective in the regulation of the chloride channel, or (4) defect in the transport of chloride ions. The most common mutation, a deletion of a phenylalanine residue at amino acid position 508 (AFjog), results in misfolding of the protein it consequently does not traffic to the membrane. 

Impaired membrane transport mechanisms can have very serious consequences. One of the best understood examples of dysfunctional transport occurs in cystic fibrosis. Cystic fibrosis (CF), a fatal autosomal recessive disease, is... 

Racial and ethnic groups may also vary in the extent to which they are carriers of autosomal recessive or dominant diseases that could be inherited by offspring. African Americans will be subject to many of the same diseases as whites, for example, cystic fibrosis, but the incidence of the disease may vary. In some cases, however, the incidence of disease may be higher among African Americans, just as it is for some white subgroups, for example, the higher incidence of Tay-Sachs disease and BRCA1 and -2 mutations in Ashkenazi Jews. 

Individuals with a family history of an autosomal or X-linked recessive disease may wish to know whether they are a heterozygous carrier of the disease. This can be established by genetic diagnosis (e.g., for cystic fibrosis, hemochromatosis, PKU, or albinism). In some specific cases, a population at high risk for a specific disease may be screened for carrier status using genetic diagnosis (e.g., Tay-Sachs disease in the Jewish population [see Clinical Correlate]). 

Bayesian probabilities are absolutely reliant upon an accurate family history of the disease in question. Family history affects the prior or a priori likelihood that a propositus is a carrier for a genetic disease. Because many hereditary disorders are autosomal recessives and manifest rarely in a sibship, any record of a known hereditary disorder can be important in providing an accurate risk reduction. This can be particularly important in cystic fibrosis, where one of the mutations is often known in affected individuals while the other is often private and uncharacterized. Fven an affected first cousin can boost the a priori probability in a Caucasian non-Jew from 1/241 to 1/8. 

Prenatal diagnosis and carrier detection of cystic fibrosis Cystic fibrosis is an autosomal recessive genetic disease resulting from mutations in the cystic fibrosis transmembrane regulator (CFTR)... 

Cystic fibrosis is a lethal autosomal recessive disorder in Caucasians, with an incidence of 1 2000 in the general population. Newborn babies with this disease have increased serum trypsin concentrations. Thus, Crossley et al. developed a radioimmunoassay for human trypsin in dried blood samples on filter paper and used it for neonatal screening for this disease (C9). A non-isotopic immunoassay, such as enzyme immunoassay of trypsin, will be developed for this purpose. 

Single-gene (also called Mendefian) disorders number more than 6000, with an incidence of about 1 in 200 births. Some examples include cystic fibrosis, sickle ceU anaemia, Marfan syndrome, Huntington s disease and hereditary haemochromatosis. Single-gene disorders are inherited in recognisable patterns autosomal dominant, autosomal recessive and X-hnked. 

Cystic fibrosis is a heterogeneous, autosomal recessive genetic disease associated with abnormal exocrine gland function, which affects multiple organs, including the gastrointestinal, pulmonary, and reproductive systems. Cystic fibrosis is... 

Cystic fibrosis is an autosomal, recessive genetic disease with an increase of 1/2000 in Caucasian births. It is the most common lethal, inherited disease among Caucasians 50% of the victims of this disease survive to 16 years and only 2% to age 35. Heterozygotes carrying the CF gene make up about 5% of the United States population but do not express the disease. 

Cystic fibrosis is relatively common, being encountered in I/I6(X) Caucasian births. It is an autosomal recessive condition. Around one in twenty-two of the population arc carriers, making the dis-ca.se one of the most common serious genetic abnonnalities. The disease affects c. iK-rine secretions, and the onset of the disease may be at birth or later in child-h(KKi. Newborn screening has been largely unsuccessful, and traditional confirmation of the disea.se depended on the demonstration of an increased chloride concentration in a. sample of sweat. 

Cystic fibrosis (CFTR gene) Inheritance autosomal recessive Location chromosome 7 (7q31) Mutation deletion of 3 bp at codonSOS accounts for 70% of mutations Huntington disease ... 

If a characteristic is inherited by autosomal dominant inheritance (ADI) (Ziegler and K6nig 2006) then it is sufficient for an individual to have inherited the relevant allele for the phenotypic characteristic associated with it to be expressed. Examples of diseases that are ADI are Huntington s chorea and myotonic dystrophy. Being autosomal, the relevant loci is on one of the 22 pairs of autosomes and hence males and females are equally affected. For autosomal recessive inheritance (ARI), it is necessary for two copies of the relevant alleles (one from each parent) to be inherited. An example of an ARI disease is cystic fibrosis. Other forms of inheritance, X-chromosomal both dominant and recessive (of which haemophilia is famously an example) and Y-chromosomal are discussed in Ziegler and Konig (2006) but will not be considered here. 

Esophageal varices in children are a manifestation of portal hypertension that causes hepatofugal flow through esophageal collateral veins to drain into the superior vena cava. The most common children s diseases that cause portal hypertension include umhilical venous catheterization, biliary atresia, alpha-1 antitrypsin deficiency, autosomal recessive polycystic renal disease and cystic fibrosis. 

Cystic fibrosis is the most common inherited fatal disease in individuals of Caucasian descent in the United States. Inherited in an autosomal-recessive fashion, the incidence of cystic fibrosis ranges from 1 in 569 in an Ohio Amish community (1) to 1 in 2500 in individuals of generalized Northern European descent (2). The incidence of cystic fibrosis is considerably lower in African-American populations with a reported frequency of 1 in 17,000 (3). 

Cystic fibrosis (CF) is a common form of an autosomal recessive genetic disease within the Caucasian population. The mutant gene lacks three base pairs (bp) in... 

Cystic fibrosis (CF) is a genetic disease caused by mutations to the gene coding the cystic fibrosis transmembrane conductance regulator (CFTR) protein in many epithelial cells and blood cells. It is the most common autosomal recessive disorder in Caucasians and affects approximately 28,000 patients in the United States and approximately 36,000 patients in Europe. An estimated 70,000 people worldwide have CF. The life expectancy of patients with CF has risen steadily over the last 25 years, from a median predicted age of survival of 25 years in 1985 to 37 years in 2011. Since in the United States an orphan disease is defined as an disease afflicting fewer than 100,000 patients, CF is an orphan disease, and ivacaftor (Kalydeco, 1) is an orphan drug. The drug is also known as a personalized medicine because CF affects about only 70,000 people worldwide. 

Two diseases causing steatorrhea deserve further attention cystic fibrosis and sprue. Cystic fibrosis is a hereditary dysfunction of the mucous and serous exocrine glands (lung, pancreas, salivary gland, sweat glands, etc.) and is sometimes associated with cirrhosis of the liver. The disease has been described mainly in whites, rarely in Negroes. Cystic fibrosis is probably transmitted by an autosomal recessive mammalian gene. 

---