Refinement of genotype-phenotype correlation in 18 patients carrying a 1q24q25 deletion
Nicolas Chatron
(1)
,
Véronique Haddad
(2)
,
Joris Andrieux
(3)
,
Julie Desir
(4)
,
Odile Boute
(5)
,
Anne Dieux
(5)
,
Clarisse Baumann
(6)
,
Séverine Drunat
(6)
,
Marion Gérard
(7)
,
Céline Bonnet
(8)
,
Bruno Leheup
(9, 8)
,
Marianne Till
(1, 10)
,
Massimiliano Rossi
(11, 10)
,
Elisabeth Flori
(12)
,
Yves Alembik
(13)
,
Helen Stewart
(14)
,
Joanna Mcparland
(14)
,
Laura Bernardini
(15)
,
Pia Castelluccio
(15, 16)
,
Laura Roos
(17)
,
Zeynep Tümer
(17)
,
Kerry Fagan
(18)
,
Anna Hackett
(18)
,
Nicole Bain
(18)
,
Arie van Haeringen
(19)
,
Claudia Ruivenkamp
(20)
,
Brigitte Benzacken
(21, 2)
,
Damien Sanlaville
(1, 11)
,
Patrick Edery
(10, 11)
,
Azzedine Aboura
(2, 22)
,
Caroline Schluth Schluth-Bolard
(23, 1)
1
Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon]
2 Unité de Cytogénétique [CHU Debré]
3 Laboratoire de Génétique Médicale
4 I.P.G. - Institut de Pathologie et Génétique [Gosselies]
5 Service de Génétique clinique
6 Unité de Génétique Clinique [CHU Debré]
7 Service de Génétique [CHU Caen]
8 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
9 Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy]
10 Service de génétique [Hôpial Louis Pradel - HCL]
11 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
12 Laboratoire de Cytogénétique
13 Service de Génétique Clinique [Hautepierre Strasbourg]
14 Department of Clinical Genetics [Churchill Hospital]
15 Mendel Laboratory
16 Ospedale Cardarelli
17 Department of Clinical Genetics [Copenhagen]
18 UoN - University of Newcastle [Callaghan, Australia]
19 Department of Clinical Genetics, Leiden University Medical Centre
20 Clinical Cytogeneticist Laboratory for Diagnostic Genome Analysis [Leiden University Medical Center]
21 Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement
22 Unité de Cytogénétiqué, Hôpital Jean-Verdier
23 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
2 Unité de Cytogénétique [CHU Debré]
3 Laboratoire de Génétique Médicale
4 I.P.G. - Institut de Pathologie et Génétique [Gosselies]
5 Service de Génétique clinique
6 Unité de Génétique Clinique [CHU Debré]
7 Service de Génétique [CHU Caen]
8 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
9 Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy]
10 Service de génétique [Hôpial Louis Pradel - HCL]
11 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
12 Laboratoire de Cytogénétique
13 Service de Génétique Clinique [Hautepierre Strasbourg]
14 Department of Clinical Genetics [Churchill Hospital]
15 Mendel Laboratory
16 Ospedale Cardarelli
17 Department of Clinical Genetics [Copenhagen]
18 UoN - University of Newcastle [Callaghan, Australia]
19 Department of Clinical Genetics, Leiden University Medical Centre
20 Clinical Cytogeneticist Laboratory for Diagnostic Genome Analysis [Leiden University Medical Center]
21 Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement
22 Unité de Cytogénétiqué, Hôpital Jean-Verdier
23 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
Céline Bonnet
- Fonction : Auteur
- PersonId : 1136608
Damien Sanlaville
- Fonction : Auteur
- PersonId : 760022
- ORCID : 0000-0001-9939-2849
- IdRef : 059247878
Patrick Edery
- Fonction : Auteur
- PersonId : 910302
Caroline Schluth Schluth-Bolard
- Fonction : Auteur
- PersonId : 774839
- IdRef : 099490145
Résumé
Interstitial deletion 1q24q25 is a rare rearrangement associated with intellectual disability, growth retardation, abnormal extremities and facial dysmorphism. In this study, we describe the largest series reported to date, including 18 patients (4M/14F) aged from 2 days to 67 years and comprising two familial cases. The patients presented with a characteristic phenotype including mild to moderate intellectual disability (100%), intrauterine (92%) and postnatal (94%) growth retardation, microcephaly (77%), short hands and feet (83%), brachydactyly (70%), fifth finger clinodactyly (78%) and facial dysmorphism with a bulbous nose (72%), abnormal ears (67%) and micrognathia (56%). Other findings were abnormal palate (50%), single transverse palmar crease (53%), renal (38%), cardiac (38%), and genital (23%) malformations. The deletions were characterized by chromosome microarray. They were of different sizes (490 kb to 20.95 Mb) localized within chromosome bands 1q23.3-q31.2 (chr1:160797550-192912120, hg19). The 490 kb deletion is the smallest deletion reported to date associated with this phenotype. We delineated three regions that may contribute to the phenotype: a proximal one (chr1:164,501,003-167,022,133), associated with cardiac and renal anomalies, a distal one (chr1:178,514,910-181,269,712) and an intermediate 490 kb region (chr1:171970575-172460683, hg19), deleted in the most of the patients, and containing DNM3, MIR3120 and MIR214 that may play an important role in the phenotype. However, this genetic region seems complex with multiple regions giving rise to the same phenotype.