The Medical Genetics Unit

Transcription

1 EPIDEMIOLOGY AND PREVENTION OF HAEMOGLOBINOPATHIES Steps needed to move forward in Italy. A professional point of view The Medical Genetics Unit 5 th EUR PEAN SYMP SIUM N RARE ANAEMIAS Ferrara - Castello Estense Novembre 2013 Dr.ssa ANNA RAVANI Laboratorio di Genetica Molecolare Unità Operativa di Genetica Medica Direttore Prof.ssa Alessandra Ferlini Azienda Ospedaliero Universitaria S.Anna FERRARA

2 MEDICAL GENETIC NETWORK IN EMILIA-ROMAGNA REGION

3 Clinical Genetics: The Genetic Counselling for Hemoglobinopathies (Dr.ssa Stefania Bigoni - Hemoglobinopathies Clinic) YEAR POSTNATAL PRENATAL

4 30% Impact of Genetic Counselling for Hemoglobinopathies in Clinical Genetics activities 30%

5 Genetic counselling: Origin of the patients

6 MEDICAL GENETIC NETWORK IN EMILIA-ROMAGNA REGION

7 Impact of diagnostics for Hemoglobinopathies in the context of the Molecular Genetics Laboratory Molecular analysis for hemoglobinopathies began in the Ferrara in 1985, with indirect test (RFLP) In 1989 started the direct analysis of the b globin gene mutations

8 Domenica Taruscio Istituto Superiore di Sanità Via Giano della Bella, Roma (I) Telefono: Fax: taruscio@iss.it ISS : Test Genetici : Qualità : Il controllo esterno di qualità dell'iss National Evaluators for b-thalassemia External Quality Scheme: Prof. M.Cristina Rosatelli Medical Sciences and Byotechnologies Departement - Cagliari Dr. Anna Ravani Molecular Genetics Laboratory U.O Medical Genetics Ferrara Hospital

9 Best Practice Guidelines for Molecular Genetic Testing Haemoglobinopathies 2002 Traeger-Synodinos J., Old J.M., Petrou M. EMQN Haemoglobinopathies 2012 September EMQN Workshop in Leiden

10 WHICH TYPES OF DIAGNOSTICS CAN FERRARA LAB OFFER? Beta globin gene: identification of point mutation (bthalassemia and Hemoglobin variants) and large rearrangements Alpha globin genes: identification of known deletions, of point mutation ( thalassemia and Hemoglobin variant) and large rearrangements METHODS ( RDB ) Known Mutation Detection Complete Sequence of all the genes ( promoter-3 UTR ) Delta globin gene: differential diagnosis upon suspicion of b or thalassemia Deletion identification in the gene and in the cluster Gamma globin genes: identification of point mutation (modifier gene in thalassemia intermedia) and F Hemoglobin variants Rearrangements and del/dup identifications in control regions (LCR and HS) by MLPA

11 Molecular diagnoses of haemoglobinopathies performed in Molecular Genetics Lab of Ferrara ( 2012 (1989 Beta Thalassemia 5123 Alpha thalassemia 1001 Delta globin gene variants Gamma globin genes variants

12 Year Total b thalassemia bth Po Delta Area bth Italy bth Immigrants (20%) 101(28%) 188(52%) Total (27%) 2573(50%) 1180(23%) Beta Thalassaemia subjects characterization in 24 years of molecular analysis

13 Changes during the years of the origins of patiens undergoing molecular diagnosis of Hemoglobinopathies % 21% 36% TOTAL Po Delta Area Southern Italy/Largest Islands Immigrants

14 b T H A L P R E N A T A L D I A G N O S E S Year b th prenatal diagnoses Origins: Po Delta Area Origins: Southern Italy and major Italian Islands Immigrating population Affected foetuses (43%) 35 TOTAL (21.6%) 1411 (66%) 259 (12% tot) 521 (24.5 %)

15 :. diagnosesmolecularoflota This allows us to make some researches on that material. Many peculiar cases have been reported in national and international conferences Two recent examples: 1 We identified a new Hemoglobin variant in two sisters affered to the Pediatric Department of our Hospital (Prof.ssa Borgna). The excellent cooperation between the two hospital units has allowed the pubblication of the case. HBB: c.406g>a p.ala135thr

16 2 We studied a AD family with high Hemoglobin A2 but normal hematological parameters. We identified a deletion involving a large part of G gene, never described before, segregating in the family with the anomalous amount of HbA2. We are now describing the new finding.

17 ..AND THE FUTURE? NEW TECHNOLOGIES ARE READY: NGS FOR HEMOGLOBINOPATHIES TESTING? The globin genes are small, probably may not require a high throughput methodology, but a very interesting application could be the contestual analysis of modifier genes, in order to interpretate peculiar phenotypes and to performe more correct prognoses. Hypotesis of analysis: Beta globin gene AND alpha globin genes, gamma globin genes, EKLF, polymorphsms at BCL11A locus and HBSIL- MYB intergenic region and so on.. Genetic modifiers of β-thalassemia and clinical severity as assessed by age at first transfusion. Danjou F, Anni F, Perseu L, Satta S, Dessì C, Lai ME, Fortina P, Devoto M, Galanello R. - Haematologica Jul;97(7):

18 All this means that our work is very hard and challenging, but it s also so fun!!

19 I thank you all for your attention