Refinement of genotype-phenotype correlation in 18 patients carrying a 1q24q25 deletion.
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.
Hospices Civils de Lyon, Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Bron, France.
Nicolas
N
Chatron
Véronique
V
Haddad
Joris
J
Andrieux
Julie
J
Désir
Odile
O
Boute
Anne
A
Dieux
Clarisse
C
Baumann
Séverine
S
Drunat
Marion
M
Gérard
Céline
C
Bonnet
Bruno
B
Leheup
Marianne
M
Till
Massimiliano
M
Rossi
Elisabeth
E
Flori
Yves
Y
Alembik
Helen
H
Stewart
Joanna
J
McParland
Laura
L
Bernardini
Pia
P
Castelluccio
Laura
L
Roos
Zeynep
Z
Tümer
Kerry
K
Fagan
Anna
A
Hackett
Nicole
N
Bain
Arie
A
van Haeringen
Claudia
C
Ruivenkamp
Brigitte
B
Benzacken
Damien
D
Sanlaville
Patrick
P
Edery
Azzedine
A
Aboura
Caroline
C
Schluth-Bolard
D000015:Abnormalities, Multiple / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype
1q24q25 deletion; DNM3; brachydactyly; growth retardation; intellectual disability