SRPX2 mutations in disorders of language cortex and cognition

Roll, Patrice; Rudolf, Gabrielle; Pereira, Sandrine; Royer, Barbara; Scheffer, Ingrid E.; Massacrier, Annick; Valenti, Maria-Paola; Roëckel-Trevisiol, Nathalie; Jamali, Sarah; Béclin, Christophe; Seegmüller, Caroline; Metz‐Lutz, Marie‐Noëlle; Lemainque, Arnaud; Délépine, Marc; Caloustian, Christophe; Saint‐Martin, Anne de; Bruneau, Nadine; Depétris, D.; Matteï, Marie‐Geneviève; Flori, Elisabeth; Robaglia-Schlupp, Andrée; Lévy, Nicolas; Neubauer, Bernd A.; Ravid, Rivka; Marescaux, Christian; Berkovic, Samuel F.; Hirsch, Édouard; Lathrop, M.; Cau, Pierre; Szepetowski, Pierre

doi:10.1093/hmg/ddl035

Cited by 251 publications

(193 citation statements)

References 20 publications

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“…These include mutations in the CNTNAP2, FOXP1 FOXP2 and SRPX2 genes. [13][14][15][16][17]42,43 In this series, 7/9 patients presented with behavioural troubles and 6 of them with ADHD, which could be explained by hemizygosity of ELKS/ECR1, located in the smallest region of overlap, given the similarity in the patients' phenotype. However, other genes expressed in the brain comprised in the microdeletion, such as CACNA1C, could also in part explain the phenotype.…”

Section: De Novomentioning

confidence: 68%

“…6,10,11 Other causative genes were secondarily described, associating speech disorders to neurobehavioural abnormalities, including the CNTNAP2, FOXP1 and SRPX2 genes. [12][13][14][15][16][17] Herein, we report on a series of nine patients with 12p subtelomeric deletions, including two familial cases with severe speech sound disorders, defined as CAS/DVD when evaluated. We therefore aimed to further clinically delineate the '12p13.33 microdeletion syndrome' and determined the smallest region of overlap and a candidate gene for speech sound disorders strongly suggesting CAS/DVD.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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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 o5 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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Section: De Novomentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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“…Environmental causes of polymicrogyria include infections during pregnancy and intrauterine ischemia [28]. Genetic causes of polymicrogyria include deletions or rearrangements of chromosomic material involving several genes (Table 2) [1,4,6,7,11,13,17,21,22,23].…”

Section: Discussionmentioning

confidence: 99%

Unilateral Opercular Polymicrogyria in a Girl with 22q13 Deletion Syndrome

Papetti¹,

Ursitti²,

Pimpolari³

et al. 2017

IJPCC

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The 22q13 deletion syndrome, also known as Phelan-McDermid Syndrome (PMS), is a chromosomal microdeletion syndrome characterized by neonatal hypotonia, normal growth, profound developmental delay, absent or delayed speech, and minor dysmorphic features. Almost all of the 22q13 deletions published so far have been described as terminal. It is believed that the SHANK3 gene is the major candidate gene for the neurologic features of the syndrome.Neuroradiological findings in PMS include arachnoid cyst, delayed myelination, frontal lobe hypoplasia, hypogenesis of corpus callosum and ventriculomegaly.We describe a 3-year-old girl with severe developmental delay and right opercular polymicrogyria associated with 22q13.2 -22q13.33 deletion.

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“…The SRPX2 gene, located on the X-chromosome, was previously implicated in EAS since a missense variant was found to co-segregate with seizures and CAS in one family (Roll et al 2006). However, all family members who experience seizures were subsequently found to have a GRIN2A mutation and no further SRPX2 mutations have been reported in EAS Reinthaler et al 2014).…”

Section: Epilepsy-aphasia Spectrum Disordersmentioning

confidence: 99%

Insights into the Genetic Foundations of Human Communication

2015

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The human capacity to acquire sophisticated language is unmatched in the animal kingdom. Despite the discontinuity in communicative abilities between humans and other primates, language is built on ancient genetic foundations, which are being illuminated by comparative genomics. The genetic architecture of the language faculty is also being uncovered by research into neurodevelopmental disorders that disrupt the normally effortless process of language acquisition. In this article, we discuss the strategies that researchers are using to reveal genetic factors contributing to communicative abilities, and review progress in identifying the relevant genes and genetic variants. The first gene directly implicated in a speech and language disorder was FOXP2. Using this gene as a case study, we illustrate how evidence from genetics, molecular cell biology, animal models and human neuroimaging has converged to build a picture of the role of FOXP2 in neurodevelopment, providing a framework for future endeavors to bridge the gaps between genes, brains and behavior.

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SRPX2 mutations in disorders of language cortex and cognition

Cited by 251 publications

References 20 publications

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

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

Unilateral Opercular Polymicrogyria in a Girl with 22q13 Deletion Syndrome

Insights into the Genetic Foundations of Human Communication

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