12p13.33 microdeletion including ELKS/ERC1, a new locus associated with childhood apraxia of speech.
Speech sound disorders are heterogeneous conditions, and sporadic and familial cases have been described. However, monogenic inheritance explains only a small proportion of such disorders, in particular in cases with childhood apraxia of speech (CAS). Deletions of <5 Mb involving the 12p13.33 locus is one of the least commonly deleted subtelomeric regions. Only four patients have been reported with such a deletion diagnosed with fluorescence in situ hybridisation telomere analysis or array CGH. To further delineate this rare microdeletional syndrome, a French collaboration together with a search in the Decipher database allowed us to gather nine new patients with a 12p13.33 subtelomeric or interstitial rearrangement identified by array CGH. Speech delay was found in all patients, which could be defined as CAS when patients had been evaluated by a speech therapist (5/9 patients). Intellectual deficiency was found in 5/9 patients only, and often associated with psychiatric manifestations of various severity. Two such deletions were inherited from an apparently healthy parent, but reevaluation revealed abnormal speech production at least in childhood, suggesting variable expressivity. The ELKS/ERC1 gene, which encodes for a synaptic factor, is found in the smallest region of overlap. These results reinforce the hypothesis that deletions of the 12p13.33 locus may be responsible for variable phenotypes including CAS associated with neurobehavioural troubles and that the presence of CAS justifies a genetic work-up.
Centre de Génétique et Centre de Référence «Anomalies du Développement et Syndromes Malformatifs», Hôpital d'Enfants, CHU Dijon, Dijon, France.
Julien
J
Thevenon
Patrick
P
Callier
Joris
J
Andrieux
Bruno
B
Delobel
Albert
A
David
Sylvie
S
Sukno
Delphine
D
Minot
Laure
L
Mosca Anne
Nathalie
N
Marle
Damien
D
Sanlaville
Marlène
M
Bonnet
Alice
A
Masurel-Paulet
Fabienne
F
Levy
Lorraine
L
Gaunt
Sandra
S
Farrell
Cédric
C
Le Caignec
Annick
A
Toutain
Virginie
V
Carmignac
Francine
F
Mugneret
Jill
J
Clayton-Smith
Christel
C
Thauvin-Robinet
Laurence
L
Faivre
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001072:Apraxias / Q000209:etiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12; D005190:Family; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007805:Language Development Disorders / Q000235:genetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011247:Pregnancy; D013060:Speech
D048868:Adaptor Proteins, Signal Transducing; C468925:ERC1 protein, human; D009419:Nerve Tissue Proteins