Presentation on theme: "Cystic Fibrosis - Clinical and Genetic Aspects"— Presentation transcript:
1 Cystic Fibrosis - Clinical and Genetic Aspects This PowerPoint file contains a number of slides that may be useful for teaching of genetics concepts.You may use these slides and their contents for non-commercial educational purposes.
2 Cystic Fibrosis This presentation contains: Clinical manifestations of CF.Clinical photographs and X-rays.Molecular genetic basis of CF, including the structure of the CFTR gene, PCR and sequencing.Examples of pedigrees and explanation of risk calculation.CF Case scenario.
3 Cystic fibrosisAffects 1 in 2,500 babies in the UK (240 babies annually)Recessively inheritedLifelong, life-limiting illnessAffects the lungs, digestive tract and pancreas by clogging them with thick, sticky mucusDaily physiotherapy, dietary supplements and intensive treatment for chest infectionsTalk through bullet pointsNotes:In CF, there is a problem transporting chloride across cell membranesCF can affect the baby before birth causing babies to be born with blocked intestines (meconium ileus)Treatment aims to improve nutrition and reduce chest infections
4 Cystic Fibrosis (1)Commonest AR-inherited disease amongst Northern European CaucasiansIncidence in UK Caucasian population 1 in 2,500 carrier risk 1 in 25Incidence in UK Asian population 1 in 10,000 carrier risk 1 in 50
5 Cystic Fibrosis (2)Gland secretions thicker or more viscous than normalSmall bowel: obstruction (meconium ileus in the newborn)Lungs : thick bronchial mucous, recurrent chest infections, progressive lung damage, heart/lung transplantation
6 Cystic Fibrosis (3)Pancreas: failure to secrete digestive enzymes causing malabsorption, failure of growth and late developmentMen nearly always infertile – absence/atrophy of vas deferensLifelong potentially fatal disease
7 Cystic Fibrosis Gene Large gene encoding 1480 amino acids Over 1,100 different mutations identified in the geneRoutinely test for 29 commonest mutationsIf mutation/s not found in clinically affected child - send DNA to laboratory to be tested for rarer mutations
8 Cystic fibrosis gene mutations Commonest mutation – Delta F508UK Caucasians - 75%UK Asians - 29%Common mutation found in 1 in 10 UK Asians - Y569D (substitution G - T)Delta F508 and 28 others account for 85% mutations in the Northern European Caucasian population
14 PSally6.4.79James9.6.76adoptedPaulAaron3.7.84Helen1.5.74RuthRobertJuneGeorged 42 yrsRTAHarry3.9.93JaneSally (1999):7 weeks pregnant, niece recently diagnosed with Cystic FibrosisEmergency referral by GP (by telephone)Drawing up the family tree allows the clinician to accurately assess the risk to Sallys baby. Sally and her partner would need to be referred to a regional clinical genetics unit to be offered counselling and carrier testing .Awareness of the inheritance pattern in CF (Autosomal Recessive) would lead the clinician to conclude that Ruth and Robert are both obligate carriers, they must both carry the altered gene in order for Jane to be affected. Therefore Sally has a carrier risk of 1:2 (50 %) as either George or June must have carried the altered gene in order to pass it on. Enquiring about ethnic origin is important because if James is Caucasian his carrier risk would be 1:22 ( 4%) .The risk to the baby of being affected would therefore be approximately 1:176.