cf case studies frances bond west midlands regional genetics laboratory 15/10/08 scobec &...
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CF Case StudiesCF Case Studies
Frances Bond
West Midlands Regional Genetics Laboratory
15/10/08
SCOBEC & Birmingham Case Studies Training Day
CasesCases
• Case 1- CM & AK– Echogenic bowel carrier testing referral
• Case 2 – RC– Meconium ileus diagnostic referral
Case 1 – CM & AKCase 1 – CM & AK• Pregnant women and partner
– CF carrier tests - Echogenic bowel
Case 1 – CM & AKCase 1 – CM & AK
• 0.1-0.2% of pregnancies
• Several causes including:– Normal variant - with no apparent cause
• Resolves itself with no known effect on the health of the child– Prenatal manifestation of meconium ileus
• ~11% of CF-affected foetuses
• ~1.3% of foetuses with echogenic bowel have CF– Can vary to up ~6% due to the subjectivity of diagnosing
echogenic bowel
Echogenic Bowel
Case 1 – CM & AKCase 1 – CM & AKARMS29
• CM and AK both p. Phe508del heterozygotes
Upper controls
Lower controls
p. Phe508del allele
Normal allele atp. Phe508del locus
Case 1 – CM & AKCase 1 – CM & AK
• At least 1 in 4 risk foetus affected with CF– Offer to test amniocentesis sample to determine CF status of
foetus if required
Case 1 – CM & AKCase 1 – CM & AK
• Amniocentesis sample tested to determine the CF status of the foetus– Unfortunately, MCC testing inconclusive
• Cultured amniocytes– ARMS29 assay: p. Phe508del heterozygote– No evidence of MCC
Prenatal Test
Case 1 – CM & AKCase 1 – CM & AK
• Foetus is a carrier of cystic fibrosis but is not predicted to be affected– Cytogenetic and QF-PCR results also negative
– Sadly, foetus spontaneously aborted soon after
Case 2 - RCCase 2 - RC
• 8 day old male• CF diagnosis test – meconium ileus
Case 2 - RCCase 2 - RCARMS29
• p. Phe508del and p. Arg117His compound heterozygote
Upper controls
Lower controls
p. Arg117His allele
p. Phe508del allele
Normal allele atp. Phe508del locus
Case 2 - RCCase 2 - RC
PolyT assay• Effect of p. Arg117His mutation is modulated by size
of polyT tract
• Heterozygous for 5T and 9T alleles
9T allele
5T allele
7T allele
C = ControlP = Patient RC
Case 2 - RCCase 2 - RC
Interpretation– p.Phe508del muation always in cis with 9T allele
– 5T allele must be in cis with p.Arg117His
• Classical CF with pancreatic sufficiency
Case 2 - RCCase 2 - RC
• Not diagnosed as part of neonatal screening programme– Average IRT result: 64 – below cut-off for molecular analysis
– IRT testing known to be inaccurate in cases with meconium ileus