Available PGD indications for monogenic disorders in the CHU of Montpellier

In France, some PGD indications are only performed in our center (retinoblastoma, spinocerebellar ataxia type I and Angelman syndrome among others). For other indications (such as cystic fibrosis and Duchenne muscular dystrophy), we have developed powerful unreported protocols in order to accept in our PGD program most of the couples requesting PGD for these conditions. Finally, for other families, we have set up techniques enabling to distinguish healthy embryos from monosomic embryos (for the chromosome studied). Thus, the embryologist may select for transfer, among a large cohort of unaffected embryos, the embryo(s) displaying the best morpholgy and kinetics of development. Consequently, the rates of pregnancy are improved.

Other PCR-based PGD protocols are being developed to provide an opportunity for couples to rapidly being accepted in our PGD program, provided that the genetic condition has been previously accepted by the multidisciplinary network licensed for PGD.

Duchenne muscular dystrophy (DMD)

Spinal muscular atrophy (SMN1)

Myotonic dystrophy (DMPK)

Hemophilia A (F8)

Spinocerebellar ataxia type I (SCAI)

Huntington disease (IT15)

von Hippel-Lindau disease (VHL)

Cystic fibrosis (CFTR)

Adenomatous polyposis coli (APC)

Hereditary retinoblastoma (RB1)

Fragile X syndrome (FMR1)

Marfan syndrome (FBN1)

Direct and indirect diagnosis

Deletion of exons 7 and 8 and indirect diagnosis

CTG repeats and indirect diagnosis

Indirect diagnosis

CAG repeats and indirect diagnosis

CAG repeats and indirect diagnosis

Exclusion testing

Direct and indirect diagnosis

F508del and G542X mutations and indirect diagnosis

Direct and indirect diagnosis

Direct and indirect diagnosis

Indirect diagnosis

Direct and indirect diagnosis

Dystonia (DYT1)

Direct and indirect diagnosis

Angelman syndrome (UBE3A)

Direct and indirect diagnosis

PGD team :

Anne Girardet (MCU-PH) - anne.girardet@inserm.fr

Céline Fernandez (technician) - celine.fernandez@inserm.fr

Publications

Girardet A, Fernandez C, Claustres M. Efficient strategies for preimplantation genetic diagnosis of spinal muscular atrophy. Fertil Steril. 2008 Aug;90(2) : 443.e7-12. Epub 2007 Oct 22. PMID :  17953949

Girardet A, Claustres M. Preimplantation genetic diagnosis and monogenic diseases. In "Molecular genetic analysis of rare diseases in 2007: selected examples". Invited review. Research signpost book (2008).

Girardet A, Moncla A, Hamamah S, Claustres M. Strategies for preimplantation genetic diagnosis of Angelman syndrome caused by mutations in UBE3A gene. RBM Online 10 :519-526 (2005).

Déchaud H, Anahory T, Girardet A, Coubes C, Cacheux V, Hamamah S, Claustres M. Diagnostic pré-implantatoire. EMC - Gynécologie Obstétrique 1: 76-87 (2004)

Girardet A, Hamamah S, Déchaud H, Anahory T, Coubes C, Hedon B, Demaille J, Claustres M. Specific detection of deleted and non-deleted dystrophin exons together with gender assignment in preimplantation genetic diagnosis of Duchenne muscular dystrophy. Mol Hum Reprod 9: 421-427 (2003)

Girardet A, Cathala P, Claustres M. Rapid detection of the DF508 mutation in single cells using DHPLC : implications for preimplantation genetic diagnosis. J Assist Reprod Genet 20: 151-154 (2003)

Girardet A, Hamamah S, Anahory T, Déchaud H, Sarda P, Hedon B, Demaille J, Claustres M. First preimplantation genetic diagnosis of hereditary retinoblastoma using informative microsatellite markers. Mol Hum Reprod 9: 111-116 (2003)

Hamamah S, Anahory T, Déchaud H, Girardet A, Blanchet P, Coubes C, Hédon B, Sarda P, Claustres M, Demaille J. Le diagnostic génétique pré-implantatoire : état des lieux 12 ans après. Reprod Hum Horm 7: 545-551 (2002)

Girardet A, Pellestor F, Claustres M. Mise au point des conditions d’amplification de l’ADN unicellulaire. Med/Sci 15: 86-89 (1999)