Genetics Resource (GRC) Rawalpindigrcpk.com/wp-content/uploads/2014/10/Prenatal... · Genetics...
Transcript of Genetics Resource (GRC) Rawalpindigrcpk.com/wp-content/uploads/2014/10/Prenatal... · Genetics...
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Maj Gen (R) Suhaib Ahmed, HI (M)MBBS; MCPS; FCPS; PhD (London)
Genetics Resource Centre (GRC)Rawalpindi
www.grcpk.com
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G ti Di dGenetic Disorders• Chromosomal Defects• Chromosomal Defects
– Trisomies (Trisomy 21 Down’s syndrome)– Monosomies (45,X Turner syndrome)
D l ti– Deletions• Single Gene Defects
– Autosomal• Recessive (Thalassaemia)• Dominant (Achondroplasia)
– X‐linked (Haemophilia)• Polygenic Defects
– Diabetes, IHD, Peptic Ulcer etc.
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Importance of Medical GeneticsImportance of Medical Genetics
Prenatal periodpA chromosomal abnormality is present in 50% of all 1st trimester pregnancy losses
Neonatal period% f ll t h t l t j it l b lit2‐3% of all neonates have at least one major congenital abnormality
2% of all neonates have a chromosomal abnormalityChildhood
50% of all cases of blindness, deafness, and severe mental retardation are due 5 , ,to genetic factorsA significant proportion of all childhood hospital admissions and deaths are due to genetic disorders
Adult lifeAdult life10% of all common cancers have a strong hereditary componentBy age 25, 5% of the population will have a disorder in which genetic factors play an important role
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Burden of Diseases in PakistanBurden of Diseases in Pakistan• Communicable Diseases: 38.4%
– Infectious and Parasitic diseases 20.4%– Respiratory Infections 8.1%– Childhood Cluster 6.7%– Sexually Transmitted 2.2%– Tropical Cluster 1.0%p
• Non‐Communicable Diseases: 37.7%– Cardiovascular 10.0%– Nutritional/Endocrine 5.8%
M li N l %– Malignant Neoplasms 4.3%– Digestive System 3.4%– Chronic Respiratory 2.6%– Neuro‐Psychiatric 3.2%– Congenital Abnormalities 3.5%– Other Non‐Communicable 4.9%
• Maternal and Perinatal Conditions: 12.5%– Maternal 2.8%Maternal 2.8%– Perinatal 9.7%
• Injuries: 11.4%
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Of the 5000 known Genetic Disorders2500 can be diagnosed by Genetic Analysis
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Di i f G ti Di dDiagnosis of Genetic Disorders
• Prenatal• Postnatal• Postnatal
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Prevention of Genetic Disorders
CarrierCarrier Screening
P t lG ti Prenatal Diagnosis
Genetic Counselling
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80
100
SARDINIA
40
60SARDINIAGREECEITALYUK
0
20CYPRUS
74 76 78 80 82 84
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Prenatal Diagnosis of Genetic DisordersPrenatal Diagnosis of Genetic Disorders
Identify Couple at Risk
Pregnancy
Fetal Sampling
Lab DiagnosisAffected Fetus Normal Fetus
Termination of PregnancTermination of Pregnancy
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l i iPrenatal Diagnosis
1. Technical feasibility2. Religious, Social & Cost Issues2. Religious, Social & Cost Issues
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F t l S liFetal Sampling
Invasive techniquesCord Blood SamplingAmniocentesisChorionic Villus Sampling (CVS)
N I i T h iNon Invasive TechniquesFetal cells in maternal bloodFetal DNA in maternal bloodFetal DNA in maternal blood
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PrimerID:
MutationsPooled:
AmplifiedProduct size:ID: Pooled: Product size:
AD-1 Fr 8-9 (+G)IVSI-5 (G-C)Fr 41-42 (-TTCT)IVSI-1 (G-T)
l b
215 bp285 bp439 bp280 bp
bDel 619bp 242 bp
AD-2 Cd 5 (-CT)Fr 16 (-C)IVSI-1 (G-T)
205 bp238 bp280 bp
Cd 30 (G-C)Cd 30 (G-A)IVSII-1 (G-A)
280 bp280 bp634 bp
AD-3 Cd 15 (G-A) 500 bpCap+1 (A-C) 567 bp
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Misdiagnosis in Prenatal DiagnosisMisdiagnosis in Prenatal Diagnosis(<0.5%)
• Maternal Contamination in Fetal Sample• PCR FailurePCR Failure• Clerical Mistakes
M i i C• Meiotic Crossover
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P t l Di i i P ki tPrenatal Diagnosis in Pakistan
• First Prenatal Diagnosis• 1st may 1994 at AFIPO h • Over 1000 each year• AFIP Rawalpindi• AKU Karachi• AKU Karachi• PNS Shifa Karachi• NIBD Karachi• NIBGE Faisalabad• GRC Rawalpindi
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Prenatal Diagnosis at GRCPrenatal Diagnosis at GRC
• Chromosomal defects• Chromosomal defects– Down syndrome (Trisomy 21)– Trisomy 13 and 18
• Single gene disorders– Thalassaemia– Cystic fibrosisCystic fibrosis– Haemophilia– Duchenne muscular dystrophyOth– Others
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P t l di i t GRC (2012 2013)Prenatal diagnosis at GRC (2012‐2013)
100
60
80
20
40
0
Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul
Thalassaemia
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Prenatal DiagnosisPrenatal Diagnosis
• Is the test required?• Is the test required?• CVS at 10‐16 weeks gestation• Average reporting time – one weekAverage reporting time one week• Complications of CVS 1‐2%• Error rate – 0.5%
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l i i i kiPrenatal Diagnosis in Pakistan
Required: 20,000/yearDone: 1000/year (5.0%)y 5
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Prenatal DiagnosisPrenatal Diagnosis
1. Technical feasibility2. Religious, Social & Cost Issues2. Religious, Social & Cost Issues
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Termination of PregnancyTermination of Pregnancy
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Termination of Pregnancy
16
Termination of Pregnancy
121416
6810
024
10 11 12 13 14 15 16 17 18 19 20 21
Accepted Refused
(S. Ahmed et al 2000)
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Prenatal Diagnosis:Prenatal Diagnosis:Reasons for under‐utilization•Did not know 23%•Expensive 23%•No access 17%•Delay in seeking 16%Ad i d i t %•Advised against 12%•Religious beliefs 9% •Other reasons 9%Other reasons 9%
(S. Naseem et al, 2008)
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Cost of Prenatal DiagnosisUK £500 (Rs. 80,000)Pakistan (GRC): Rs. 5000
Indigenous PCR kitsMultiplexing in PCRI di PCR i tIndigenous PCR equipment
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DNA Lab Made in PakistanDNA Lab Made in Pakistan
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DNA Lab Made in PakistanDNA Lab Made in Pakistan
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Communicable diseases& Malnutrition Genetic disorders
Present HealthPriority
High infant mortality(90/1000)
I i ti Primary Health N t itiImmunization Primary HealthCare
Nutrition
Fall in infant mortality(< 40/1000)(< 40/1000)
Genetic disorders Commnicable diseases& Malnutrition
Future HealthPriority
Treatment(very costly) Prevention
(S. Ahmed 1998)
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18
12
14
16s.
Policy-1
4
6
8
10
t in
billio
ns o
f Rs
Policy-2
0
2
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Number of years from the start of policy
Cos
t
Number of years from the start of policy
(S. Ahmed 1998)