TY - JOUR
T1 - Genotype-phenotype relationship in a child with 2.3Mb de novo interstitial 12p13.33-p13.32 deletion
AU - Fanizza, Isabella
AU - Bertuzzo, Sara
AU - Beri, Silvana
AU - Scalera, Elisabetta
AU - Massagli, Angelo
AU - Sali, Maria Enrica
AU - Giorda, Roberto
AU - Bonaglia, Maria Clara
PY - 2014
Y1 - 2014
N2 - Microdeletion 12p13.33, though very rare, is an emerging condition associated with variable phenotype including a specific speech delay sound disorder, labelled childhood apraxia of speech (CAS), intellectual disability (ID) and neurobehavioral problems.Here we report a de novo 2.3Mb interstitial 12p13.33-p13.32 deletion in a 5 year-old child with mild ID, speech delay, microcephaly, muscular hypotonia, and joint laxity. In contrast to previously reported patients with 12p13.33 monosomy, our patient's interstitial deletion spans the 12p13.33-12p13.32 region with the distal breakpoint within intron 12 of CACNA1C.Phenotype-genotype comparison between our case, previously reported patients, and subjects with 12p13.33 deletions led us to propose that haploinsufficiency of CACNA1C may influence the variability of the patients' phenotype, since the gene resulted disrupted or entirely deleted in the majority of reported patients. In addition, phenotypic features such as microcephaly, muscular hypotonia, and joint laxity are mainly present in patients with monosomy of 12p13.33 extending to the 12p13.32 portion. A common region of ~300kb, harbouring EFCAB4B and PARP11, is deleted in patients with microcephaly while a second region of ~700kb, including TSPAN9 and PMTR8, could be associated with muscle hypotonia and joint laxity. These data reinforce the hypothesis that multiple haploinsufficient genes and age-dependent observation may concur to generate the variable phenotype associated with 12p13.33 deletion.
AB - Microdeletion 12p13.33, though very rare, is an emerging condition associated with variable phenotype including a specific speech delay sound disorder, labelled childhood apraxia of speech (CAS), intellectual disability (ID) and neurobehavioral problems.Here we report a de novo 2.3Mb interstitial 12p13.33-p13.32 deletion in a 5 year-old child with mild ID, speech delay, microcephaly, muscular hypotonia, and joint laxity. In contrast to previously reported patients with 12p13.33 monosomy, our patient's interstitial deletion spans the 12p13.33-12p13.32 region with the distal breakpoint within intron 12 of CACNA1C.Phenotype-genotype comparison between our case, previously reported patients, and subjects with 12p13.33 deletions led us to propose that haploinsufficiency of CACNA1C may influence the variability of the patients' phenotype, since the gene resulted disrupted or entirely deleted in the majority of reported patients. In addition, phenotypic features such as microcephaly, muscular hypotonia, and joint laxity are mainly present in patients with monosomy of 12p13.33 extending to the 12p13.32 portion. A common region of ~300kb, harbouring EFCAB4B and PARP11, is deleted in patients with microcephaly while a second region of ~700kb, including TSPAN9 and PMTR8, could be associated with muscle hypotonia and joint laxity. These data reinforce the hypothesis that multiple haploinsufficient genes and age-dependent observation may concur to generate the variable phenotype associated with 12p13.33 deletion.
KW - 12p13.33 Deletion
KW - Array-CGH
KW - CACNA1C
KW - Interstitial deletion
KW - Microcephaly
KW - Speech delay
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U2 - 10.1016/j.ejmg.2014.04.009
DO - 10.1016/j.ejmg.2014.04.009
M3 - Article
C2 - 24780630
AN - SCOPUS:84902167449
VL - 57
SP - 334
EP - 338
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
SN - 1769-7212
IS - 7
ER -