MOLECULAR SCREENING OF ADAMTSL2 GENE IN 33 PATIENTS REVEALS THE GENETIC HETEROGENEITY OF GELEOPHYSIC DYSPLASIA
Slimane Allali
(1)
,
Carine Le Goff
(1)
,
Isabelle Pressac-Diebold
(1)
,
Gwendolyne Pfenning
(1)
,
Clã©mentine Mahaut
(1)
,
Nathalie Dagoneau
(1)
,
Yasemin Alanay
(2)
,
Angela F. Brady
(3)
,
Yanick J. Crow
(4)
,
Koen Devriendt
(5)
,
Valérie Drouin-Garraud
(6)
,
Elisabeth Flori
(7)
,
David Genevieve
(8)
,
Raoul C. Hennekam
(9)
,
Jane A Hurst
(10)
,
Deborah Krakow
(11)
,
Martine Le Merrer
(1)
,
K. D. Lichtenbelt
(12)
,
Sally A. Lynch
(13)
,
Stanislas Lyonnet
(1)
,
K. Macdermot
(14)
,
Sahar Mansour
(15)
,
André Mégarbané
(16)
,
Heloisa G. Santos
(17)
,
Miranda Splitt
(18)
,
Andrea Superti-Furga
(19)
,
Sheila Unger
(19)
,
Denise Williams
(20)
,
Arnold Munnich
(1)
,
Valerie Cormier-Daire
(1)
1
Inserm U781 -
Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement
2 Ankara University School of Medicine [Turkey]
3 North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow
4 Genetic Medicine, University of Manchester, Manchester Academic Heath Science Centre
5 Department of Medical Genetics, Leuven University Hospital, Leuven
6 Hôpital Charles Nicolle [Rouen]
7 Department of genetics, Strasbourg hospital, Strasbourg
8 Service de Génétique Médicale
9 Department of Pediatrics, Academic Medical Center, University of Amsterdam
10 Departement of Clinical Genetics, Oxford Radcliffe Hospitals
11 Cedars-Sinai Medical Center
12 UMCU - University Medical Center [Utrecht]
13 National Center for Medical Genetics, Dublin
14 North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow
15 SW Thames Regional Genetics Service, St Georgeâ™s University of London, London
16 USJ - Université Saint-Joseph de Beyrouth
17 Department of Medical Genetics , Lisboa
18 Institute of Human Genetics, Newcastle
19 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
20 Birmingham women's hospital, Birmingham
2 Ankara University School of Medicine [Turkey]
3 North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow
4 Genetic Medicine, University of Manchester, Manchester Academic Heath Science Centre
5 Department of Medical Genetics, Leuven University Hospital, Leuven
6 Hôpital Charles Nicolle [Rouen]
7 Department of genetics, Strasbourg hospital, Strasbourg
8 Service de Génétique Médicale
9 Department of Pediatrics, Academic Medical Center, University of Amsterdam
10 Departement of Clinical Genetics, Oxford Radcliffe Hospitals
11 Cedars-Sinai Medical Center
12 UMCU - University Medical Center [Utrecht]
13 National Center for Medical Genetics, Dublin
14 North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow
15 SW Thames Regional Genetics Service, St Georgeâ™s University of London, London
16 USJ - Université Saint-Joseph de Beyrouth
17 Department of Medical Genetics , Lisboa
18 Institute of Human Genetics, Newcastle
19 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
20 Birmingham women's hospital, Birmingham
Slimane Allali
- Fonction : Auteur
- PersonId : 907865
Carine Le Goff
- Fonction : Auteur
- PersonId : 907866
Isabelle Pressac-Diebold
- Fonction : Auteur
- PersonId : 907867
Gwendolyne Pfenning
- Fonction : Auteur
- PersonId : 907868
Clã©mentine Mahaut
- Fonction : Auteur
- PersonId : 907869
Nathalie Dagoneau
- Fonction : Auteur
- PersonId : 907870
Angela F. Brady
- Fonction : Auteur
- PersonId : 907872
Yanick J. Crow
- Fonction : Auteur
- PersonId : 11918
- IdHAL : yanick-crow
- ORCID : 0000-0001-7211-7564
- IdRef : 227205359
Koen Devriendt
- Fonction : Auteur
- PersonId : 907027
Elisabeth Flori
- Fonction : Auteur
- PersonId : 907873
David Genevieve
- Fonction : Auteur
- PersonId : 907874
- ORCID : 0000-0001-6928-6287
- IdRef : 068913532
Raoul C. Hennekam
- Fonction : Auteur
- PersonId : 907022
Jane A Hurst
- Fonction : Auteur
- PersonId : 907875
Martine Le Merrer
- Fonction : Auteur
- PersonId : 902649
Stanislas Lyonnet
- Fonction : Auteur
- PersonId : 895056
K. Macdermot
- Fonction : Auteur
- PersonId : 907879
Sahar Mansour
- Fonction : Auteur
- PersonId : 904443
Andrea Superti-Furga
- Fonction : Auteur
- PersonId : 907882
Sheila Unger
- Fonction : Auteur
- PersonId : 907883
Arnold Munnich
- Fonction : Auteur
- PersonId : 886441
Valerie Cormier-Daire
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 907865
Connectez-vous pour contacter l'auteur
Résumé
Geleophysic dysplasia (OMIM 231050, GD) is an autosomal recessive disorder characterized by short stature, small hands and feet, stiff joints and thick skin. Patients often present with a progressive cardiac valvular disease which can lead to an early death. In a previous study including six GD families, we have mapped the disease gene on chromosome 9q34.2 and identified mutations in the A Disintegrin And Metalloproteinase with Thrombospondin repeats-like 2 gene (ADAMTSL2). Following this study, we have collected the samples of 30 additional GD families, including 33 patients and identified ADAMTSL2 mutations in 14/33 patients, comprising 13 novel mutations. The absence of mutation in 19 patients prompted us to compare the two groups of GD patients, namely group 1, patients with ADAMTSL2 mutations (n=20, also including the 6 patients from our previous study) and group 2, patients without ADAMTSL2 mutations (n=19). We found that the main discriminating features were facial dysmorphism and tip-toe walking, almost constantly observed in group 1. No differences were found concerning heart involvement, skin thickness, recurrent respiratory and ear infections, bronchopulmonary insufficiency, laryngo-tracheal stenosis, deafness and radiographic features. We conclude that GD is a genetically heterogeneous condition. Ongoing studies will hopefully lead to the identification of another disease gene.
Format du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
MOLECULAR SCREENING OF ADAMTSL2 GENE IN 33 PATIENTS REVEALS THE GENETIC HETEROGENEITY OF GELEOPHYSIC DYSPLASIA
|
Résumé |
en
Geleophysic dysplasia (OMIM 231050, GD) is an autosomal recessive disorder characterized by short stature, small hands and feet, stiff joints and thick skin. Patients often present with a progressive cardiac valvular disease which can lead to an early death. In a previous study including six GD families, we have mapped the disease gene on chromosome 9q34.2 and identified mutations in the A Disintegrin And Metalloproteinase with Thrombospondin repeats-like 2 gene (ADAMTSL2). Following this study, we have collected the samples of 30 additional GD families, including 33 patients and identified ADAMTSL2 mutations in 14/33 patients, comprising 13 novel mutations. The absence of mutation in 19 patients prompted us to compare the two groups of GD patients, namely group 1, patients with ADAMTSL2 mutations (n=20, also including the 6 patients from our previous study) and group 2, patients without ADAMTSL2 mutations (n=19). We found that the main discriminating features were facial dysmorphism and tip-toe walking, almost constantly observed in group 1. No differences were found concerning heart involvement, skin thickness, recurrent respiratory and ear infections, bronchopulmonary insufficiency, laryngo-tracheal stenosis, deafness and radiographic features. We conclude that GD is a genetically heterogeneous condition. Ongoing studies will hopefully lead to the identification of another disease gene.
|
Auteur(s) |
Slimane Allali
1
, Carine Le Goff
1
, Isabelle Pressac-Diebold
1
, Gwendolyne Pfenning
1
, Clã©mentine Mahaut
1
, Nathalie Dagoneau
1
, Yasemin Alanay
2
, Angela F. Brady
3
, Yanick J. Crow
4
, Koen Devriendt
5
, Valérie Drouin-Garraud
6
, Elisabeth Flori
7
, David Genevieve
8
, Raoul C. Hennekam
9
, Jane A Hurst
10
, Deborah Krakow
11
, Martine Le Merrer
1
, K. D. Lichtenbelt
12
, Sally A. Lynch
13
, Stanislas Lyonnet
1
, K. Macdermot
14
, Sahar Mansour
15
, André Mégarbané
16
, Heloisa G. Santos
17
, Miranda Splitt
18
, Andrea Superti-Furga
19
, Sheila Unger
19
, Denise Williams
20
, Arnold Munnich
1
, Valerie Cormier-Daire
1
1
Inserm U781 -
Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement
( 2827 )
- Gh Necker - Enfants Malades 149, Rue de Sevres 75743 PARIS CEDEX 15
- France
2
Ankara University School of Medicine [Turkey]
( 495747 )
- Hacettepe Mahallesi A.Adnan Saygun Cad. No: 35 06100 Altndağ/Ankara/Turkey
- Turquie
3
North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow
( 164797 )
- France
4
Genetic Medicine, University of Manchester, Manchester Academic Heath Science Centre
( 164798 )
- France
5
Department of Medical Genetics, Leuven University Hospital, Leuven
( 164799 )
- France
6
Hôpital Charles Nicolle [Rouen]
( 300106 )
- CHU de Rouen
1 rue de Germont, 76031 Rouen cedex
- France
7
Department of genetics, Strasbourg hospital, Strasbourg
( 164801 )
- France
8
Service de Génétique Médicale
( 164802 )
- Hôpital Arnaud de Villeneuve, Montpellier
- France
9
Department of Pediatrics, Academic Medical Center, University of Amsterdam
( 164803 )
- Pays-Bas
10
Departement of Clinical Genetics, Oxford Radcliffe Hospitals
( 164804 )
- Royaume-Uni
11
Cedars-Sinai Medical Center
( 324147 )
- 8700 Beverly Blvd, Los Angeles, California 90048
- États-Unis
12
UMCU -
University Medical Center [Utrecht]
( 73956 )
- Heidelberglaan 100
3584 CX Utrecht
- Pays-Bas
13
National Center for Medical Genetics, Dublin
( 164807 )
- Irlande
14
North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow
( 164808 )
- Royaume-Uni
15
SW Thames Regional Genetics Service, St Georgeâ™s University of London, London
( 164809 )
- Royaume-Uni
16
USJ -
Université Saint-Joseph de Beyrouth
( 301405 )
- Rectorat de l'USJ
Rue de Damas, BP 17-5208 - Mar Mikhaël
Beyrouth - 1104 2020
- Liban
17
Department of Medical Genetics , Lisboa
( 164811 )
- Portugal
18
Institute of Human Genetics, Newcastle
( 164812 )
- France
19
CHUV -
Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
( 329903 )
- Rue du Bugnon 21
CH-1011 Lausanne, Vaud
- Suisse
20
Birmingham women's hospital, Birmingham
( 164814 )
- France
|
Comité de lecture |
Oui
|
Vulgarisation |
Non
|
Langue du document |
Anglais
|
Nom de la revue |
|
Date de production/écriture |
2010-11-25
|
Audience |
Internationale
|
Date de publication |
2011-03-17
|
Volume |
48
|
Numéro |
6
|
Page/Identifiant |
417
|
Mots-clés |
en
Genetics, Clinical genetics, Connective tissue disease
|
DOI | 10.1136/jmg.2010.087544 |
Pubmed Id | 21415077 |
Origine :
Fichiers produits par l'(les) auteur(s)
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