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Case Reports
. 2013 Jan;21(1):82-8.
doi: 10.1038/ejhg.2012.116. Epub 2012 Jun 20.

12p13.33 microdeletion including ELKS/ERC1, a new locus associated with childhood apraxia of speech

Julien Thevenon  1 , Patrick Callier, Joris Andrieux, Bruno Delobel, Albert David, Sylvie Sukno, Delphine Minot, Laure Mosca Anne, Nathalie Marle, Damien Sanlaville, Marlène Bonnet, Alice Masurel-Paulet, Fabienne Levy, Lorraine Gaunt, Sandra Farrell, Cédric Le Caignec, Annick Toutain, Virginie Carmignac, Francine Mugneret, Jill Clayton-Smith, Christel Thauvin-Robinet, Laurence Faivre
Affiliations
Case Reports

12p13.33 microdeletion including ELKS/ERC1, a new locus associated with childhood apraxia of speech

Julien Thevenon et al. Eur J Hum Genet. 2013 Jan.

Abstract

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.

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Figures

Figure 1
Figure 1
Photos of patients 1, 3 and 9. Note the mild non-specific dysmorphic features. Patient 1: macrocephaly, square and coarse face with large forehead, enophtalmia, down-slanting palpebral fissures, low-set ears, anteverted and thick ear lobes, a marked philtrum, large nares, a thin upper lip and irregular and narrowly spaced teeth; patient 3: no dysmorphic features; and patient 9: hypotelorism, horizontal eyebrows, up-slanting palpebral fissures, large nares and downturned corner of the mouth. Photos published with parental consent.
Figure 2
Figure 2
Alignment of the deletions identified with array CGH. The first four megabases from the telomere comprise 35 genes. Four of them are known genes expressed in the brain and implicated in neurotransmission (IQSEC3 and ELKS/ERC1) or have been assigned to psychotic phenotypes (SLC6A13 and CACNA1C). The smallest region of overlap in all the patients with speech delay (260 kb) only contains the ELKS/ERC1 gene.
See this image and copyright information in PMC

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