Brain calcifications and PCDH12 variants

Gaël Nicolas, Monica Sanchez-Contreras, Eliana Marisa Ramos, Roberta R. Lemos, Joana Ferreira, Denis Moura, Maria J. Sobrido, Anne Claire Richard, Alma Rosa Lopez, Andrea Legati, Jean François Deleuze, Anne Boland, Olivier Quenez, Pierre Krystkowiak, Pascal Favrole, Daniel H. Geschwind, Adi Aran, Reeval Segel, Ephrat Levy-Lahad, Dennis W Dickson & 3 others Giovanni Coppola, Rosa V Rademakers, João R.M. De Oliveira

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Abstract

Objective: To assess the potential connection between PCDH12 and brain calcifications in a patient carrying a homozygous nonsense variant in PCDH12 and in adult patients with brain calcifications. Methods: We performed a CT scan in 1 child with a homozygous PCDH12 nonsense variant. We screened DNA samples from 53 patients with primary familial brain calcification (PFBC) and 26 patients with brain calcification of unknown cause (BCUC). Results: We identified brain calcifications in subcortical and perithalamic regions in the patient with a homozygous PCDH12 nonsense variant. The calcification pattern was different from what has been observed in PFBC and more similar to what is described in in utero infections. In patients with PFBC or BCUC, we found no protein-truncating variant and 3 rare (minor allele frequency <0.001) PCDH12 predicted damaging missense heterozygous variants in 3 unrelated patients, albeit with no segregation data available. Conclusions: Brain calcifications should be added to the phenotypic spectrum associated with PCDH12 biallelic loss of function, in the context of severe cerebral developmental abnormalities. A putative role for PCDH12 variants remains to be determined in PFBC.

Original languageEnglish (US)
JournalNeurology: Genetics
Volume3
Issue number4
DOIs
StatePublished - Jan 1 2017

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Brain
Gene Frequency
DNA
Infection
Proteins

ASJC Scopus subject areas

  • Clinical Neurology
  • Genetics(clinical)

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Nicolas, G., Sanchez-Contreras, M., Ramos, E. M., Lemos, R. R., Ferreira, J., Moura, D., ... De Oliveira, J. R. M. (2017). Brain calcifications and PCDH12 variants. Neurology: Genetics, 3(4). https://doi.org/10.1212/NXG.0000000000000166

Brain calcifications and PCDH12 variants. / Nicolas, Gaël; Sanchez-Contreras, Monica; Ramos, Eliana Marisa; Lemos, Roberta R.; Ferreira, Joana; Moura, Denis; Sobrido, Maria J.; Richard, Anne Claire; Lopez, Alma Rosa; Legati, Andrea; Deleuze, Jean François; Boland, Anne; Quenez, Olivier; Krystkowiak, Pierre; Favrole, Pascal; Geschwind, Daniel H.; Aran, Adi; Segel, Reeval; Levy-Lahad, Ephrat; Dickson, Dennis W; Coppola, Giovanni; Rademakers, Rosa V; De Oliveira, João R.M.

In: Neurology: Genetics, Vol. 3, No. 4, 01.01.2017.

Research output: Contribution to journalArticle

Nicolas, G, Sanchez-Contreras, M, Ramos, EM, Lemos, RR, Ferreira, J, Moura, D, Sobrido, MJ, Richard, AC, Lopez, AR, Legati, A, Deleuze, JF, Boland, A, Quenez, O, Krystkowiak, P, Favrole, P, Geschwind, DH, Aran, A, Segel, R, Levy-Lahad, E, Dickson, DW, Coppola, G, Rademakers, RV & De Oliveira, JRM 2017, 'Brain calcifications and PCDH12 variants', Neurology: Genetics, vol. 3, no. 4. https://doi.org/10.1212/NXG.0000000000000166
Nicolas G, Sanchez-Contreras M, Ramos EM, Lemos RR, Ferreira J, Moura D et al. Brain calcifications and PCDH12 variants. Neurology: Genetics. 2017 Jan 1;3(4). https://doi.org/10.1212/NXG.0000000000000166
Nicolas, Gaël ; Sanchez-Contreras, Monica ; Ramos, Eliana Marisa ; Lemos, Roberta R. ; Ferreira, Joana ; Moura, Denis ; Sobrido, Maria J. ; Richard, Anne Claire ; Lopez, Alma Rosa ; Legati, Andrea ; Deleuze, Jean François ; Boland, Anne ; Quenez, Olivier ; Krystkowiak, Pierre ; Favrole, Pascal ; Geschwind, Daniel H. ; Aran, Adi ; Segel, Reeval ; Levy-Lahad, Ephrat ; Dickson, Dennis W ; Coppola, Giovanni ; Rademakers, Rosa V ; De Oliveira, João R.M. / Brain calcifications and PCDH12 variants. In: Neurology: Genetics. 2017 ; Vol. 3, No. 4.
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AU - Sanchez-Contreras, Monica

AU - Ramos, Eliana Marisa

AU - Lemos, Roberta R.

AU - Ferreira, Joana

AU - Moura, Denis

AU - Sobrido, Maria J.

AU - Richard, Anne Claire

AU - Lopez, Alma Rosa

AU - Legati, Andrea

AU - Deleuze, Jean François

AU - Boland, Anne

AU - Quenez, Olivier

AU - Krystkowiak, Pierre

AU - Favrole, Pascal

AU - Geschwind, Daniel H.

AU - Aran, Adi

AU - Segel, Reeval

AU - Levy-Lahad, Ephrat

AU - Dickson, Dennis W

AU - Coppola, Giovanni

AU - Rademakers, Rosa V

AU - De Oliveira, João R.M.

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N2 - Objective: To assess the potential connection between PCDH12 and brain calcifications in a patient carrying a homozygous nonsense variant in PCDH12 and in adult patients with brain calcifications. Methods: We performed a CT scan in 1 child with a homozygous PCDH12 nonsense variant. We screened DNA samples from 53 patients with primary familial brain calcification (PFBC) and 26 patients with brain calcification of unknown cause (BCUC). Results: We identified brain calcifications in subcortical and perithalamic regions in the patient with a homozygous PCDH12 nonsense variant. The calcification pattern was different from what has been observed in PFBC and more similar to what is described in in utero infections. In patients with PFBC or BCUC, we found no protein-truncating variant and 3 rare (minor allele frequency <0.001) PCDH12 predicted damaging missense heterozygous variants in 3 unrelated patients, albeit with no segregation data available. Conclusions: Brain calcifications should be added to the phenotypic spectrum associated with PCDH12 biallelic loss of function, in the context of severe cerebral developmental abnormalities. A putative role for PCDH12 variants remains to be determined in PFBC.

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