prikaz prve stranice dokumenta Genotype–phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder
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Scientific paper - Review paper
Genotype–phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder
Human Genetics, 142 (2023), 7; 909-925. https://doi.org/10.1007/s00439-023-02552-2
D’Onofrio, Gianluca; Accogli, Andrea; Severino, Mariasavina; Caliskan, Haluk; Kokotović, Tomislav; Blažeković, Antonela; Gotovac Jerčić, Kristina; Markovic, Silvana; Žigman, Tamara; Goran, Krnjak; Barišić, Nina; Duranovic, Vlasta; Ban, Ana; Borovečki, Fran; Petković Ramadža, Danijela; Barić, Ivo; Fazeli, Walid; Herkenrath, Peter; Marini, Carla; Vittorini, Roberta; Gowda, Vykuntaraju; Bouman, Arjan; Rocca, Clarissa; Alkhawaja, Issam Azmi; Murtaza, Bibi Nazia; Rehman, Malik Mujaddad Ur; Al Alam, Chadi; Nader, Gisele; Mancardi, Maria Margherita; Giacomini, Thea; Srivastava, Siddharth; Alvi, Javeria Raza; Tomoum, Hoda; Matricardi, Sara; Iacomino, Michele; Riva, Antonella; Scala, Marcello; Madia, Francesca; Pistorio, Angela; Salpietro, Vincenzo; Minetti, Carlo; Rivière, Jean-Baptiste; Srour, Myriam; Efthymiou, Stephanie; Maroofian, Reza; Houlden, Henry; Vernes, Sonja Catherine; Zara, Federico; Striano, Pasquale; Nagy, Vanja More authors...

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D’Onofrio, G., Accogli, A., Severino, M., Caliskan, H., Kokotović, T., Blažeković, A. ... Nagy, V. (2023). Genotype–phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder. Human Genetics, 142. (7), 909-925. doi: 10.1007/s00439-023-02552-2

D’Onofrio, Gianluca, et al. "Genotype–phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder." Human Genetics, vol. 142, no. 7, 2023, pp. 909-925. https://doi.org/10.1007/s00439-023-02552-2

D’Onofrio, Gianluca, Andrea Accogli, Mariasavina Severino, Haluk Caliskan, Tomislav Kokotović, Antonela Blažeković, Kristina Gotovac Jerčić, et al. "Genotype–phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder." Human Genetics 142, no. 7 (2023): 909-925. https://doi.org/10.1007/s00439-023-02552-2

D’Onofrio, G., et al. (2023) 'Genotype–phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder', Human Genetics, 142(7), pp. 909-925. doi: 10.1007/s00439-023-02552-2

D’Onofrio G, Accogli A, Severino M, Caliskan H, Kokotović T, Blažeković A, and sur.. Genotype–phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder. Human Genetics [Internet]. 2023 May 14 [cited 2024 November 15];142(7):909-925. doi: 10.1007/s00439-023-02552-2

G. D’Onofrio, et al., "Genotype–phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder", Human Genetics, vol. 142, no. 7, pp. 909-925, May 2023. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:105:335918. [Accessed: 15 November 2024]

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Metadata
Title (english)Genotype–phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder
AuthorGianluca D’Onofrio
AuthorAndrea Accogli
AuthorMariasavina Severino
AuthorHaluk Caliskan
AuthorTomislav Kokotović
AuthorAntonela Blažeković
AuthorKristina Gotovac Jerčić
AuthorSilvana Markovic
AuthorTamara Žigman
AuthorKrnjak Goran
AuthorNina Barišić
AuthorVlasta Duranovic
AuthorAna Ban
AuthorFran Borovečki
AuthorDanijela Petković Ramadža
AuthorIvo Barić
AuthorWalid Fazeli
AuthorPeter Herkenrath
AuthorCarla Marini
AuthorRoberta Vittorini
AuthorVykuntaraju Gowda
AuthorArjan Bouman
AuthorClarissa Rocca
AuthorIssam Azmi Alkhawaja
AuthorBibi Nazia Murtaza
AuthorMalik Mujaddad Ur Rehman
AuthorChadi Al Alam
AuthorGisele Nader
AuthorMaria Margherita Mancardi
AuthorThea Giacomini
AuthorSiddharth Srivastava
AuthorJaveria Raza Alvi
AuthorHoda Tomoum
AuthorSara Matricardi
AuthorMichele Iacomino
AuthorAntonella Riva
AuthorMarcello Scala
AuthorFrancesca Madia
AuthorAngela Pistorio
AuthorVincenzo Salpietro
AuthorCarlo Minetti
AuthorJean-Baptiste Rivière
AuthorMyriam Srour
AuthorStephanie Efthymiou
AuthorReza Maroofian
AuthorHenry Houlden
AuthorSonja Catherine Vernes
AuthorFederico Zara
AuthorPasquale Striano
AuthorVanja Nagy
Author's institutionUniversity of Zagreb
School of Medicine
(Department of Pediatrics)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Pediatrics
Abstract (english)
Contactin-associated protein-like 2 (CNTNAP2) gene encodes for CASPR2, a presynaptic type 1 transmembrane protein, involved in cell-cell adhesion and synaptic interactions. Biallelic CNTNAP2 loss has been associated with "Pitt-Hopkins-like syndrome-1" (MIM#610042), while the pathogenic role of heterozygous variants remains controversial. We report 22 novel patients harboring mono- (n = 2) and bi-allelic (n = 20) CNTNAP2 variants and carried out a literature review to characterize the genotype-phenotype correlation. Patients (M:F 14:8) were aged between 3 and 19 years and affected by global developmental delay (GDD) (n = 21), moderate to profound intellectual disability (n = 17) and epilepsy (n = 21). Seizures mainly started in the first two years of life (median 22.5 months). Antiseizure medications were successful in controlling the seizures in about two-thirds of the patients. Autism spectrum disorder (ASD) and/or other neuropsychiatric comorbidities were present in nine patients (40.9%). Nonspecific midline brain anomalies were noted in most patients while focal signal abnormalities in the temporal lobes were noted in three subjects. Genotype-phenotype correlation was performed by also including 50 previously published patients (15 mono- and 35 bi-allelic variants). Overall, GDD (p < 0.0001), epilepsy (p < 0.0001), hyporeflexia (p = 0.012), ASD (p = 0.009), language impairment (p = 0.020) and severe cognitive impairment (p = 0.031) were significantly associated with the presence of biallelic versus monoallelic variants. We have defined the main features associated with biallelic CNTNAP2 variants, as severe cognitive impairment, epilepsy and behavioral abnormalities. We propose CASPR2-deficiency neurodevelopmental disorder as an exclusively recessive disease while the contribution of heterozygous variants is less likely to follow an autosomal dominant inheritance pattern.
Keywords (english)
Languageenglish
Publication typeScientific paper - Review paper
Publication statusPublished
Peer reviewPeer review
Publication versionPublished version
Journal titleHuman Genetics
Numberingvol. 142, no. 7, pp. 909-925
p-ISSN0340-6717
e-ISSN1432-1203
DOIhttps://doi.org/10.1007/s00439-023-02552-2
URN:NBNurn:nbn:hr:105:335918
Publication2023-05-14
Document URLhttps://link.springer.com/10.1007/s00439-023-02552-2
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2023-10-27 08:58:07