gg2020 developing capacity for variant data sharing in low- and middle-income counties: latin...

GLOBAL GLOBIN 2020 CHALLENGEDEVELOPING CAPACITY FOR VARIANT DATA SHARING IN

LOW & MIDDLE INCOME COUNTRIES

Paris, France, 2016

GLOBAL GLOBIN 2020 CHALLENGE

DEVELOPING CAPACITY FOR VARIANT DATA SHARING IN

LOW & MIDDLE INCOME COUNTRIES Latin American Countries

Paris, France, 2016

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HbS AND BETA THALASSEMIA CARRIERS IN LATINAMERICA

País

Población Millones

% Portadores

HbS

% Portadores β-talasemia

Raíces africanas

Población General

México 120 12.8 0.45 0.4

Honduras, Nicaragua, Costa Rica, Panamá

8.7, 6.0, 4.9, 4.0

10.0, 11.1, 10.9, 16.0

NE, NE, 2.5, 7.7

NE, NE, 0.25, NE

Cuba, Haití, República Dominicana

11.0, 9.8, 10.1

6.1, 13.2, 7.0

1.5, 15.0, 4.8

0.45, 1.0, 1.0

Colombia, Venezuela 48.2, 28.0 11.2, 19.1 2.4, 1.9 0.8, 0.2

Brasil 203.4 6.2 4 1.3

Ecuador, Perú 16.3, 30.8 21.9, NE NE, 3.3 NE, 2.05

Argentina, Uruguay 41.8, 3.3 NE, 10.0 0.7, NE 1.35, NE

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Countries interested to participate in GG2020

MéxicoColombia

Costa Rica Panamá

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WHAT IS KNOWN ABOUT THE DISEASE BURDEN IN YOUR COUNTRY?

What are the major health issues related to haemoglobinopathies in your country?

Mexico Sickle cell disease and thalassemias

Colombia Pain crisis in SCD patients, the major cause of hospitalization

Costa Rica Sickle cell disease, beta thal minor and some cases of Cooley’s anemia

Panamá Sickle cell disease and thalassemias

Is there any central reporting of cases?

Mexico No

Colombia No

Costa Rica Yes. A Research Center (CIHATA) (Universidad de Costa Rica) (but it doesn't receive all the cases). It is obligatory the newborn screening on Hb S by The National Screening Program, supported by the Public Health System (Caja Costarricense del Seguro Social). There is also a Foundation from patients for additional support (called FUNDREPA)

Panamá Yes. The Health Minister for newborn Screening.

What information is readily available? What is its quality?

Mexico Academic books and national and international papers

Colombia Limited to academic texts like books and papers.

Costa Rica There are different population studies, some with molecular studies, and the first report of the neonatal screening program on HbS.

Panamá Newborn Screening Very confidencial.

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NATIONAL CO-ORDINATION AND PLANNINGIs there a national co-ordination and planning body for any haemoglobinopathies?what does it do: national epidemiology: monitor demand and supply of services: public education: other?:

Mexico No, there isn’t a national coordination center for haemoglobinopathies

Colombia No, there isn’t a national coordination center for haemoglobinopathies

Costa Rica There is no national coordination. The more precise information on HbS is obtained from the National Screening Program. Not all the samples are sent to the Research Center (CIHATA). Other hospitals do their own diagnosis. national epidemiology: population studies by CIHATA and screening program. monitor demand and supply of services: each hospital public education: by CIHATA and FUNDREPA other?

Panamá Is there a national co-ordination and planning body for any haemoglobinopathies?Yeswhat does it do: national epidemiology: monitor demand and supply of services: yes public education: Yes other?: Neonatal screening

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Local contacts

1. MéxicoDr. Augusto Rojas Martínez ([email protected]).Dra. Bertha Ibarra ([email protected]).2. Costa Rica Dr. Walter Rodríguez ([email protected])3. PanamáDra. Gladys Cossio ([email protected] )4. ColombiaDra. Laura Cifuentes ([email protected])

mailto:[email protected]





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Countries interested to participate in GG2020

BrazilUruguay

Venezuela

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WHAT IS KNOWN ABOUT THE DISEASE BURDEN IN YOUR COUNTRY?

What are the major health issues related to haemoglobinopathies in your country?

Brazil Sickle cell disease and thalassemias. Betha Globin mutations more common.

Uruguay Sickle cell anemia and thalassemia

Venezuela Sickle cell disease, beta thal minor. Haemoglobinopathy more frequent HbS, and variants C and D.

Is there any central reporting of cases?

Brazil Yes

Uruguay Central reporting cases . National Pilote Program for Haemoglobinopathies detection (Dbe 2012) Reference National Laboratorie Banco Prevision Social.

Venezuela Central Reporting cases of Congenital Diseases and rare conditions. Not for haemoglobinopathies. ECLAM.

What information is readily available? What is its quality?

Brazil National registry of reporting cases Screening programs haemoglobinopathies patients and family members. Genetic Counselling

Uruguay National Registry of Congenital Debects and rare diseases )RNDCER)http://www.msp.gub.uy/marco-normativo/registro- nacional-de- defectos-cong%C3%A9nitos- y-enfermedades- raras

Venezuela National registry of reporting cases

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BrazilIs there a national co-ordination and planning body for any haemoglobinopathies?No, there isn’t a national coordination center for haemoglobinopathiesThe Laboratory of Hemoglobinopathies in the Clinical Pathology Department of the Medical Sciences School of the State University in Campinas - Unicamp, São Paulo, Southeastern Brazil, carried out, in its 27 years of activity, about 130,000 diagnoses. E M Kimura,2014. Works specifically looking for genetic risk factors for sickle cell anemia complications, like vasooclusive events (stroke), leg ulcers, sickle cell retinopathy and pregnancy complications. We have been using microarray analysis, exome sequencing and transcriptome sequencing as our main strategiesHPLC/RP-HPLCV/multiplex ligation-dependent probe amplification (MLPA) techniques. microarray analysis, exome sequencing and transcriptome sequencing , Monica Melo

Medical and Human Genetics Laboratory (Laboratório de Genética Humana e Médica - LGHM) at the Federal University of Pará (Universidade Federal do Pará - UFPA)In quilombos communities in the Pará state studied variations in HbF levels in sickle cell anemia patients and its interaction with clinical disease, using HPLC and molecular biology (ABI 7500 Real Time PCR) for the genotyping of previously published SNPs related to such variations and Molecular characterization of patients with any suspected hemoglobinopathy , with PCR, multiplex PCR, Real Time PCR and DNA sequencing and search for mutations that cause variants hemoglobins (S and C), alfa-thalassemia (-3.7, -20.5, -MED and -SEA), beta-thalassemia (-87, -88, -29, CD6, CD15, IVSI-1, IVSI-5, IVSI-6, ....) and SNPs related to variations in HbFlevels (HBG2, BCL11A, HBS1-MYB). Our goal is to propose a research to assist disease prognosis and improvepatients’ life quality. João Farias Guerreiro Graice Cardoso,PhD

Molecular alterations responsible for the alpha-thalassemic phenotypes in 8 unrelated individuals (3 males and 5 females; age, 4 months to 30 years) in whom the molecular basis of the disease could not be determined by conventional methods were detected. Avariety of rearrangements identified, C.N. Suemasu,2011.

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Uruguay 48.000 births per year/ 2 cases yearly.

Inmunoelectroforesis globinas IEF/ HPLC adults ;

No molecular test

Is there a national co-ordination and planning body for any haemoglobinopathies?No, there isn’t a national coordination center for haemoglobinopathies.

No screening services.

No genetic counselling

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VenezuelaIn a population study of 80400 individuals from diferent regions of Venezuela with dx of haemolitic anemia:-76400 by hemoglobin electrophoresis in acetate and citrate agar, solubility tests, family studies and 4000 by cromathography (HPLC-CE)

9% have Dx of haemoglobinopathy, been the more frequent HbS, and variants C and D. Thalasemia and its relation with Hb S and C was determined.

Frequency of haplotypes of bs gen in 272 patients with drepanocitosis (SCA) and heterocygotes for HbS was 50, 8% Benin, 32,2% CAR, 14,2 Senegal y 2,3% Camerun.

In homocygous patients for HbS 8% was homocygous for Ben haplotype, 82% were double heterocygote for haplotypes Ben/CAR, 8,8% presented haplotypes Ben,Senegal,CAR/Senegal y Ben/Camerun and one patient was homocygos for haplotype CA A Arends et al, Science and Technology,2007, 32;8:516-521

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VenezuelaSickle Cell Disease SCD exhibits a wide spectrum of clinical behaviour, from mild condition to an incapacitating illness Epidemiological studies: variable frequency, ranging from zero in the Venezuelan indians up to 5% in the Mestizo and Afro-American population; 12% in the North Central costal Region (Arends,1971; Arends et al 1982).

Seven polymorphic sites in the b-globin gene cluster (State of Aragua). . Benin haplotype 0.479, Bantu haplotype 0.406; atypical Bantu A2 0.042; Senegal 0.031; atypical Bantu A7 0.021 and Saudi Arabia_Indian (0.021). N Moreno et al, Genet. Mol. Biol. 25,1:2002 Sudanese and Bantu origins for the African slaves brought into Venezuela.

Haematological characteristics and clinical severity related to variations in fetal haemoglobin (HBF) levels (Falusi and Otalungi,1994);Steimberg,1996), the simultaneous presence of a-thalassemia (Figuereido,et al,1996, Mukherjee et al, 1997) glucose-6-phosphate dehydrogenase deficiency (Bouanga et al,1998) and the b-globin cluster linked haplotypes (Powars adnHiti,1993 Steinerg 1996).

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Venezuela

•101.301 heel blood samples newborns were analysed by high performance liquid chromatography (HPLC-CE), using Variant Bio Rad System with the Sickle Cell Short program for the filter paper samples and the Beta thak program for family studies127 unrelated subjects with a suspicion of β- thalassemia trait or with a clinically recognized β-thal syndrome of different degrees of severity had DNA studies (PCR-bases reverse dot-blot method or amplification refractory mutation system (ARMS).

15 different mutations were identified accounting for the 92% of the mutant alleles studied, revealing a significant genetic heterogeneity at the β- globin gene locus in this population M Bravo-Urquiola, Hemoglobin,2012;36(3):209-18).Most frequent mutations: Codon 39 (C >T) 34.1%, IVS-I-(G >A) 11.1%, IVS-I-6(T >C=6.6%,-29 (A >G) 5.2%.Less common mutations IVS-I-5 (G >A) 3.7% The 1,393 bp deletion 3.0% IVSII-1 (G >A) 3.0%, -86 (C >G) 2.2% , IVSII-1 (G >T) 1.5%, (C >T) codons 41/42 (-TCTT) 1.5%, IVSS-II745 (C >G) 0.7% and deletion al ᶳβ- thal 0.7%.

The major sources of β - thal-alleles in Venezuela , as expected, are of Mediterranean and African origins.Diversity of haplotypes associated with some of the β-thal mutations can be explained by in situ recombination events in Venezuela. Genetic counseling as well as implementing comprehensive clinical care programs are starting now. There isn’t a national coordination center for haemoglobinopathies

As In most of the countries the Health Care System is Public. Public Education and Public Health Services. The majority of Genetics Departments or Units in the region are located in General Universitary Hospitals or Research Institutes. Genetic Counselling is part of the activity of Clinical Geneticist in the Country.

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Local contacts

1. Brazil Dr. Fernando Ferreira Costa, Dr. Sara T. Olalla Saad and Dr. Dulcinéia M. Albuquerque

Hematology and Hemotherapy Center, Faculty of Medical Sciences, University of Campinas, SP, Brazil Dr. Maria de Fátima Sonati, Dr. Magnun Nueldo Nunes dos Santos and Dr. Susan Elizabeth Domingues Costa JorgeDepartment of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, SP, Brazil

Dr. Mônica Barbosa de Melo, Human Genetics Laboratory, Center for MolecularBiology and Genetic Engineering, University of Campinas, SP, Brazil

[email protected] Dra. Greice [email protected] Professor Joao Farias Guerreiro

2. Uruguay Dra. Mariela Larrandaburu [email protected]

3. Venezuela Dra A. Arends Dra. M Bravo-Urquiola, Dra. Aída Falcón de [email protected]





Dra. Aída Falcón de Vargas President RELAGH and President VSHGDra. Lavinia Schuller Faccini Vice President of RELAGH and President BSMG

Thank You