PCDH19. This is the Epilepsiome page for PCDH19, which is associated with an X-linked sex-limited early infantile epileptic encephalopathy that primarily affects females and is characterized by brief recurrent seizure clusters, a phenotype often closely resembling Dravet syndrome.
Here are the most recent blog posts that mention PCDH19
- Mysteries of a neuronal pathfinder – this is what you should know about PCDH19 in 2015
- The OMIM epileptic encephalopathy genes – a 2014 review
- Mutation intolerance – why some genes withstand mutations and others don’t
In a nutshell. PCDH19-related epilepsy is characterized by brief recurrent seizure clusters. First clinically described in the early 1970s in families with girls affected by epilepsy, this X-linked sex-limited disorder primarily affects females, while transmitting hemizygous males are generally unaffected. This pattern is the opposite of what we usually see with X-linked inheritance. PCDH19 was eventually identified as the causative gene in 2008 and by 2015, more than 140 patients have been reported. A small number of affected males with somatic mosaicism for a pathogenic variant have since been reported with similar symptoms to affected females. Haploinsufficiency appears to be the pathogenic mechanism at the cellular level. The mechanism underlying the unique pattern of inheritance has yet to be fully explained, but it is hypothesized that it may be due to the abnormal interactions of two different PCDH19-associated neuron populations (mutant and wild-type) at the tissue level.
| Phenotypes | Genetics | Mechanism & Function |
| The Clinical Perspective | Community | Resources & References |
Schematic illustration of the cellular interference mechanism associated with PCDH19 mutations (adapted under a Creative Commons attribution from Depienne et al., 2009 http://127.0.0.1:8081/plosgenetics/article?id=info:doi/10.1371/journal.pgen.1000381)
Phenotypes
PCDH19-related epilepsy, also known as PCDH19 female epilepsy or early infantile epileptic encephalopathy type 9 (EIEE9), is a genetic early infantile epileptic encephalopathy characterized by an explosive onset of brief recurrent seizure clusters (generally lasting 1-5 minutes and repeating multiple times a day) in late infancy lasting through childhood. Seizures are often induced or exacerbated by high fever. The most common types of seizures seen in PCDH19-related epilepsy are generalized tonic, clonic or tonic-clonic, and/or focal seizures. Seizures can be so violent that they require admission to an intensive care unit and they can be refractory to antiepileptic medication. Seizure frequency decreases with age and over time, patients may become seizure-free. Most affected females have mild to severe intellectual disability and/or autism, a characteristic that contributed to the original name of the condition: epilepsy in females with mental retardation (EFMR). However, some individuals have normal cognition. The phenotype, including seizure type and EEG patterns, overlaps significantly with that of Dravet syndrome, which is often caused by pathogenic variants in SCN1A. According to some studies, PCDH19 variants are found in approximately 25% of females who present with features of Dravet syndrome and test negative for SCN1A variants. Some individuals with PCDH19-related epilepsy present with other types of epilepsy, such as Ohtahara syndrome, or other non-epilepsy phenotypes, including autism spectrum disorders or intellectual disability. Other neurological symptoms, such as ataxia, may also be present. The affected mosaic males reported thus far have clinical features similar to those seen in females.
Genetics
Mutation spectrum. Over 120 different disease-causing variants have been reported in PCDH19. Most variants are heterozygous missense or nonsense variants or small insertions or deletions located within exon 1, which encodes the entire extracellular domain of the protein. A small number of splice site variants, as well as exonic or whole gene deletions, have also been identified. Variants have been reported throughout the gene, except in exon 2. Most PCDH19 variants are unique to a single patient or family; only a few recurrent variants have been reported.
Genotype-Phenotype Correlation. PCDH19-associated epilepsy exhibits significant phenotypic variability, even within the same family. No genotype-phenotype correlations have been established thus far.
General Considerations for Variant interpretation. When reviewing a genetic variant to determine its significance for a given patient, it is important to weigh multiple pieces of evidence:
Considerations for gene level interpretation. First, it is important to establish the strength of the evidence showing that the gene is associated with epilepsy. Some genes may only have one variant reported in a single individual with epilepsy, while other genes may have multiple variants reported in many large families with an autosomal dominant pattern of epilepsy. For PCDH19, there is very strong evidence for its role in human epilepsy.
Considerations for variant level interpretation. When reviewing the significance of a variant, it is important to consider the impact on the gene and the presence of the variant in previously described patient and control populations. Many clinical genetic testing laboratories classify genetic variants into different categories, ranging from benign to pathogenic. Variants that are common in control populations and would not be predicted to have a major impact on the gene/protein are generally classified as benign. Variants are more likely to be classified as pathogenic if the variants are rare or not present in the control population, reported in multiple individuals or families with disease, and likely to have a higher impact on the gene/protein based on the type of mutation or functional studies. Variants with uncertain or limited available evidence may be classified as variants of uncertain significance (VUS), indicating that further information is required in order for the variant to be further defined. In some cases, testing additional family members can be helpful, as it allows the lab to determine whether or not the variant was inherited (versus de novo) and how the variant segregates with disease in the family. This is particularly true for PCDH19 variants, as most disease-causing variants would be expected to be de novo, inherited from an unaffected father, or inherited from an affected mother. Sometimes further classification of a VUS requires waiting for the identification of additional patients or families with similar or nearby variants.
Inheritance, Penetrance & Prevalence. The majority (~70%) of pathogenic PCDH19 variants are de novo. Inherited disease-causing variants follow an X-linked female-limited inheritance pattern: females who inherit a heterozygous pathogenic variant are affected, while hemizygous males with the variant are unaffected. The penetrance of PCDH19-associated phenotypes appears to be high in females, however, a small percentage (~3%) of females who have a disease-causing PCDH19 variant do not present with symptoms. Considerable variable expressivity can occur, even with the same variant, particularly in age of onset, seizure types and intellectual disability. Although hemizygous males are generally asymptomatic, a small number of affected mosaic males have also been reported. The exact prevalence of PCDH19-related epilepsy is unknown, however, PCDH19 does appear to be a more common cause of early infantile epileptic encephalopathies presenting with seizure clusters, particularly in females. A recent study of patients with a broader spectrum of early-onset epilepsy and/or developmental delay identified PCDH19 variants in 3 of 400 patients, suggesting that PCDH19 variants is a minor player in the broader epilepsy and developmental delay spectrum.
Mechanism & Function
Mechanism. The PCDH19-encoded protein is a protocadherin, a neuronal adhesion protein that plays an important role in early development of the central nervous system. Neurons grow and connect through cues on the surface, and cell-cell adhesion proteins are critically involved in this process. Given the known variant spectrum, which includes primarily nonsense and frameshift variants or missense variants in exon 1 that may impact the protein’s adhesive abilities, some groups have proposed a loss of function mechanism at the cellular level. It is unclear how perturbation of this mechanism leads to disease at the tissue level, but it is hypothesized that the co-existence of neurons expressing PCDH19 and neurons deficient for PCDH19 creates two populations of neurons that have problems interacting. This hypothesis is unproven, but provides a framework for why PCDH19 variants may be pathogenic in individuals with two different populations of neurons (females with random X-inactivation and mosaic males) but not in males who only have one population. The fact that non-mosaic hemizygous males do not present with seizures or intellectual disability suggests that the PCDH19-encoded protein, protocadherin 19, is non-essential in humans.
Cell/Animal models.
Mice. There is currently no mouse model for PCDH19-related epilepsy. A PCDH19-deficient mouse model could help to elucidate the proposed mechanism for disease.
Zebrafish. Zebrafish models show disorganization of parts of the optic tectum, which is the brain subdivision that mediates vision. The zebrafish mutants also have abnormalities in visually-guided behaviors but no evidence of seizures.
The Clinical Perspective
Recurrence risk & testing of family members. PCDH19 variants can be de novo or inherited in an X-linked female limited pattern. Each child of an individual with a disease-causing variant has a 50% (1 in 2) of inheriting the disease-causing variant. All female children of males who carry a disease-causing variant will inherit the variant and be expected to be affected. A small percentage of females who inherit a disease-causing variant appear to be asymptomatic. Somatic and germline mosaicism of PCDH19 variants have been reported, making the recurrence risk for families with a child with an apparent de novo variant higher than the general population risk.
Therapy.
Neurosteroids. A gene expression study by Tan and collaborators suggests that enzymes generating neurosteroids are downregulated in patients with PCDH19-FE and that patients have lower allopregnanolone levels than age-matched controls. Given that neurosteroids have strong anticonvulsant properties, the authors suggest that influencing this mechanism may be a potential therapeutic target. Dysregulation of neurosteroids may be one of the downstream consequences of PCHD19 haploinsuffiency and future research will help us understand to what extent this dysregulation is relevant in clinical practice. At this point, the role of neurosteroid is speculative and has not been tested clinically.
Corticosteroids. A small case series by Higurashi and collaborators suggests that corticosteroids may be used during seizure clusters and may lead to the short term resolution of seizures. Steroids can be powerful antiepileptic medications that are also used in other epilepsy syndromes and it will be interesting to see whether this initial finding can be replicated. Given the mentioning of neurosteroids earlier, we wanted to point out that corticosteroids are related to neurosteroids, but are different compounds.
Anti-NMDA receptor antibodies. The same case series by Higurashi and collaborators suggest that antibodies to NMDA receptors can be identified in a significant number of patients with PCDH19FE. The authors speculate about a breakdown of the blood brain barrier during seizure and a subsequent immune response that is driving the seizures. A confirmation of these findings in an independent separate study may help us judge the relevance of these findings. Currently, there is little evidence from other studies that this mechanism is relevant in PCDH19FE.
Stiripentol. A single case report by Trivisano and collaborators report suggests that stiripentol may be helpful in treatment. However, the patient reported in their study was already older (~20 years) and it is difficult to distinguish the medication effect from the spontaneous resolution of seizures that occur in some patients.
Community
Research studies. The scientific community is actively studying PCDH19 and its role in human disease. The PCDH19 Epilepsiome team is happy to facilitate if you have questions or a specific interest in this gene.
Family connections. The PCDH19 community is very active and the PCDH19 Alliance maintains a frequently updated webpage about the most recent findings and research activities regarding PCDH19 Female Epilepsy.
Patient registry. The PCDH19 community has a registry to gather information about individuals with PCDH19 variants.
Resources & References
Websites
References
Multiplex families with epilepsy: Success of clinical and molecular genetic characterization.
Afawi Z, Oliver KL, Kivity S, Mazarib A, Blatt I, Neufeld MY, Helbig KL, Goldberg-Stern H, Misk AJ, Straussberg R, Walid S, Mahajnah M, Lerman-Sagie T, Ben-Zeev B, Kahana E, Masalha R, Kramer U, Ekstein D, Shorer Z, Wallace RH, Mangelsdorf M, MacPherson JN, Carvill GL, Mefford HC, Jackson GD, Scheffer IE, Bahlo M, Gecz J, Heron SE, Corbett M, Mulley JC, Dibbens LM, Korczyn AD, Berkovic SF.
Neurology. 2016 Feb 23;86(8):713-22.
PMID:26802095
Dravet syndrome: a genetic epileptic disorder.
Akiyama M, Kobayashi K, Ohtsuka Y.
Acta Med Okayama. 2012;66(5):369-76.
PMID:23093055
Steroids efficacy in the acute management of seizure clusters in one case of PCDH19 female epilepsy.
Bertani G, Spagnoli C, Iodice A, Salerno GG, Frattini D, Fusco C.
Seizure. 2015 Nov;32:45-6.
PMID:26552561
Cognitive and behavioral profile in females with epilepsy with PDCH19 mutation: two novel mutations and review of the literature.
Camacho A, Simón R, Sanz R, Viñuela A, Martínez-Salio A, Mateos F.
Epilepsy Behav. 2012 May;24(1):134-7.
PMID:22504056
Cognitive development in females with PCDH19 gene-related epilepsy.
Cappelletti S, Specchio N, Moavero R, Terracciano A, Trivisano M, Pontrelli G, Gentile S, Vigevano F, Cusmai R.
Epilepsy Behav. 2015 Jan;42:36-40.
PMID:25499160
Characterizing PCDH19 in human induced pluripotent stem cells (iPSCs) and iPSC-derived developing neurons: emerging role of a protein involved in controlling polarity during neurogenesis.
Compagnucci C, Petrini S, Higuraschi N, Trivisano M, Specchio N, Hirose S, Bertini E, Terracciano A.
Oncotarget. 2015 Sep 29;6(29):26804-13.
PMID:26450854
Protocadherins control the modular assembly of neuronal columns in the zebrafish optic tectum.
Cooper SR, Emond MR, Duy PQ, Liebau BG, Wolman MA, Jontes JD.
J Cell Biol. 2015 Nov 23;211(4):807-14.
PMID:26598617
Molecular genetics of Dravet syndrome.
De Jonghe P.
Dev Med Child Neurol. 2011 Apr;53 Suppl 2:7-10.
PMID:21504425
Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females.
Depienne C, Bouteiller D, Keren B, Cheuret E, Poirier K, Trouillard O, Benyahia B, Quelin C, Carpentier W, Julia S, Afenjar A, Gautier A, Rivier F, Meyer S, Berquin P, Hélias M, Py I, Rivera S, Bahi-Buisson N, Gourfinkel-An I, Cazeneuve C, Ruberg M, Brice A, Nabbout R, Leguern E.
PLoS Genet. 2009 Feb;5(2):e1000381. Erratum in: PLoS Genet. 2009 Apr;5(4).
PMID:19214208
PCDH19-related infantile epileptic encephalopathy: an unusual X-linked inheritance disorder.
Depienne C, LeGuern E.
Hum Mutat. 2012 Apr;33(4):627-34.
PMID:22267240
Mutations and deletions in PCDH19 account for various familial or isolated epilepsies in females.
Depienne C, Trouillard O, Bouteiller D, Gourfinkel-An I, Poirier K, Rivier F, Berquin P, Nabbout R, Chaigne D, Steschenko D, Gautier A, Hoffman-Zacharska D, Lannuzel A, Lackmy-Port-Lis M, Maurey H, Dusser A, Bru M, Gilbert-Dussardier B, Roubertie A, Kaminska A, Whalen S, Mignot C, Baulac S, Lesca G, Arzimanoglou A, LeGuern E.
Hum Mutat. 2011 Jan;32(1):E1959-75.
PMID:21053371
Recurrence risk of epilepsy and mental retardation in females due to parental mosaicism of PCDH19 mutations.
Dibbens LM, Kneen R, Bayly MA, Heron SE, Arsov T, Damiano JA, Desai T, Gibbs J, McKenzie F, Mulley JC, Ronan A, Scheffer IE.
Neurology. 2011 Apr 26;76(17):1514-9.
PMID:21519002
X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment.
Dibbens LM, Tarpey PS, Hynes K, Bayly MA, Scheffer IE, Smith R, Bomar J, Sutton E, Vandeleur L, Shoubridge C, Edkins S, Turner SJ, Stevens C, O’Meara S, Tofts C, Barthorpe S, Buck G, Cole J, Halliday K, Jones D, Lee R, Madison M, Mironenko T, Varian J, West S, Widaa S, Wray P, Teague J, Dicks E, Butler A, Menzies A, Jenkinson A, Shepherd R, Gusella JF, Afawi Z, Mazarib A, Neufeld MY, Kivity S, Lev D, Lerman-Sagie T, Korczyn AD, Derry CP, Sutherland GR, Friend K, Shaw M, Corbett M, Kim HG, Geschwind DH, Thomas P, Haan E, Ryan S, McKee S, Berkovic SF, Futreal PA, Stratton MR, Mulley JC, Gécz J.
Nat Genet. 2008 Jun;40(6):776-81.
PMID:18469813
A novel PCDH19 mutation inherited from an unaffected mother.
Dimova PS, Kirov A, Todorova A, Todorov T, Mitev V.
Pediatr Neurol. 2012 Jun;46(6):397-400.
PMID:22633638
Epilepsy and mental retardation restricted to females: X-linked epileptic infantile encephalopathy of unusual inheritance.
Duszyc K, Terczynska I, Hoffman-Zacharska D.
J Appl Genet. 2015 Feb;56(1):49-56.
PMID:25204757
A complex of Protocadherin-19 and N-cadherin mediates a novel mechanism of cell adhesion.
Emond MR, Biswas S, Blevins CJ, Jontes JD.
J Cell Biol. 2011 Dec 26;195(7):1115-21.
PMID:22184198
PCDH19 mutations in female patients from Southern Italy.
Gagliardi M, Annesi G, Sesta M, Tarantino P, Conti P, Labate A, Di Rosa G, Quattrone A, Gambardella A.
Seizure. 2015 Jan;24:118-20.
PMID:25218114
Expression of the delta-protocadherin gene Pcdh19 in the developing mouse embryo.
Gaitan Y, Bouchard M.
Gene Expr Patterns. 2006 Oct;6(8):893-9.
PMID:16682261
Absence of layer-specific cadherin expression profiles in the neocortex of the reeler mutant mouse.
Hertel N, Redies C.
Cereb Cortex. 2011 May;21(5):1105-17.
PMID:20847152
Cadherin expression delineates the divisions of the postnatal and adult mouse amygdala.
Hertel N, Redies C, Medina L.
J Comp Neurol. 2012 Dec 1;520(17):3982-4012.
PMID:22592879
PCDH19-related female-limited epilepsy: further details regarding early clinical features and therapeutic efficacy.
Higurashi N, Nakamura M, Sugai M, Ohfu M, Sakauchi M, Sugawara Y, Nakamura K, Kato M, Usui D, Mogami Y, Fujiwara Y, Ito T, Ikeda H, Imai K, Takahashi Y, Nukui M, Inoue T, Okazaki S, Kirino T, Tomonoh Y, Inoue T, Takano K, Shimakawa S, Hirose S.
Epilepsy Res. 2013 Sep;106(1-2):191-9.
PMID:23712037
PCDH19 mutation in Japanese females with epilepsy.
Higurashi N, Shi X, Yasumoto S, Oguni H, Sakauchi M, Itomi K, Miyamoto A, Shiraishi H, Kato T, Makita Y, Hirose S.
Epilepsy Res. 2012 Mar;99(1-2):28-37.
PMID:22050978
Immediate suppression of seizure clusters by corticosteroids in PCDH19 female epilepsy.
Higurashi N, Takahashi Y, Kashimada A, Sugawara Y, Sakuma H, Tomonoh Y, Inoue T, Hoshina M, Satomi R, Ohfu M, Itomi K, Takano K, Kirino T, Hirose S.
Seizure. 2015 Apr;27:1-5.
PMID:25891919
Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families.
Hynes K, Tarpey P, Dibbens LM, Bayly MA, Berkovic SF, Smith R, Raisi ZA, Turner SJ, Brown NJ, Desai TD, Haan E, Turner G, Christodoulou J, Leonard H, Gill D, Stratton MR, Gecz J, Scheffer IE.
J Med Genet. 2010 Mar;47(3):211-6.
PMID:19752159
Characteristic phasic evolution of convulsive seizure in PCDH19-related epilepsy.
Ikeda H, Imai K, Ikeda H, Shigematsu H, Takahashi Y, Inoue Y, Higurashi N, Hirose S.
Epileptic Disord. 2016 Mar 1;18(1):26-33.
PMID:26898795
Novel de novo PCDH19 mutations in three unrelated females with epilepsy female restricted mental retardation syndrome.
Jamal SM, Basran RK, Newton S, Wang Z, Milunsky JM.
Am J Med Genet A. 2010 Oct;152A(10):2475-81.
PMID:20830798
A new familial form of convulsive disorder and mental retardation limited to females.
Juberg RC, Hellman CD.
J Pediatr. 1971 Nov;79(5):726-32.
PMID: 5116697
The expression of non-clustered protocadherins in adult rat hippocampal formation and the connecting brain regions.
Kim SY, Mo JW, Han S, Choi SY, Han SB, Moon BH, Rhyu IJ, Sun W, Kim H.
Neuroscience. 2010 Sep 29;170(1):189-99.
PMID:20541594
Cadherin expression in the somatosensory cortex: evidence for a combinatorial molecular code at the single-cell level.
Krishna-K K, Hertel N, Redies C.
Neuroscience. 2011 Feb 23;175:37-48
PMID:21129452
Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.
Kwong AK, Fung CW, Chan SY, Wong VC.
PLoS One. 2012;7(7):e41802.
PMID:22848613
Identification of four novel PCDH19 Mutations and prediction of their functional impact.
Leonardi E, Sartori S, Vecchi M, Bettella E, Polli R, Palma LD, Boniver C, Murgia A.
Ann Hum Genet. 2014 Nov;78(6):389-98.
PMID:25227595
Expression of delta-protocadherins in the spinal cord of the chicken embryo.
Lin J, Wang C, Redies C.
J Comp Neurol. 2012 May 1;520(7):1509-31.
PMID:22102158
Expression of protocadherin-19 in the nervous system of the embryonic zebrafish.
Liu Q, Chen Y, Kubota F, Pan JJ, Murakami T.
Int J Dev Biol. 2010;54(5):905-11.
PMID:19757381
Effectiveness of antiepileptic therapy in patients with PCDH19 mutations.
Lotte J, Bast T, Borusiak P, Coppola A, Cross JH, Dimova P, Fogarasi A, Graneß I, Guerrini R, Hjalgrim H, Keimer R, Korff CM, Kurlemann G, Leiz S, Linder-Lucht M, Loddenkemper T, Makowski C, Mühe C, Nicolai J, Nikanorova M, Pellacani S, Philip S, Ruf S, Sánchez Fernández I, Schlachter K, Striano P, Sukhudyan B, Valcheva D, Vermeulen RJ, Weisbrod T, Wilken B, Wolf P, Kluger G.
Seizure. 2016 Feb;35:106-10.
PMID:26820223
Focal seizures with affective symptoms are a major feature of PCDH19 gene-related epilepsy.
Marini C, Darra F, Specchio N, Mei D, Terracciano A, Parmeggiani L, Ferrari A, Sicca F, Mastrangelo M, Spaccini L, Canopoli ML, Cesaroni E, Zamponi N, Caffi L, Ricciardelli P, Grosso S, Pisano T, Canevini MP, Granata T, Accorsi P, Battaglia D, Cusmai R, Vigevano F, Dalla Bernardina B, Guerrini R.
Epilepsia. 2012 Dec;53(12):2111-9.
PMID:22946748
Protocadherin 19 mutations in girls with infantile-onset epilepsy.
Marini C, Mei D, Parmeggiani L, Norci V, Calado E, Ferrari A, Moreira A, Pisano T, Specchio N, Vigevano F, Battaglia D, Guerrini R.
Neurology. 2010 Aug 17;75(7):646-53.
PMID:20713952
Genes of early-onset epileptic encephalopathies: from genotype to phenotype.
Mastrangelo M, Leuzzi V.
Pediatr Neurol. 2012 Jan;46(1):24-31.
PMID:22196487
Protocadherin 19 mutations in girls with infantile-onset epilepsy.
Nabbout R, Depienne C, Chiron C, Dulac O.
Neurology. 2011 Mar 29;76(13):1193-4; author reply 1194.
PMID:21444909
Epilepsy with PCDH19 mutation masquerading as benign partial epilepsy in infancy.
Samanta D.
Neurol India. 2016 Mar-Apr;64(2):327-8.
PMID:26954813
Diagnosis and long-term course of Dravet syndrome.
Scheffer IE.
Eur J Paediatr Neurol. 2012 Sep;16 Suppl 1:S5-8.
PMID:22704920
Acute-onset epilepsy triggered by fever mimicking FIRES (febrile infection-related epilepsy syndrome): the role of protocadherin 19 (PCDH19) gene mutation.
Specchio N, Fusco L, Vigevano F.
Epilepsia. 2011 Nov;52(11):e172-5.
PMID:21777234
Spectrum of phenotypes in female patients with epilepsy due to protocadherin 19 mutations.
Specchio N, Marini C, Terracciano A, Mei D, Trivisano M, Sicca F, Fusco L, Cusmai R, Darra F, Bernardina BD, Bertini E, Guerrini R, Vigevano F.
Epilepsia. 2011 Jul;52(7):1251-7.
PMID:21480887
Inversion of layer-specific cadherin expression profiles and maintenance of cytoarchitectonic areas in the allocortex of the reeler mutant mouse.
Stoya G, Redies C, Schmid-Hertel N.
J Comp Neurol. 2014 Sep 1;522(13):3106-19.
PMID:24591110
Mutations of protocadherin 19 in female epilepsy (PCDH19-FE) lead to allopregnanolone deficiency.
Tan C, Shard C, Ranieri E, Hynes K, Pham DH, Leach D, Buchanan G, Corbett M, Shoubridge C, Kumar R, Douglas E, Nguyen LS, Mcmahon J, Sadleir L, Specchio N, Marini C, Guerrini R, Moller RS, Depienne C, Haan E, Thomas PQ, Berkovic SF, Scheffer IE, Gecz J.
Hum Mol Genet. 2015 Sep 15;24(18):5250-9.
PMID:26123493
Somatic mosaicism of PCDH19 mutation in a family with low-penetrance EFMR.
Terracciano A, Specchio N, Darra F, Sferra A, Bernardina BD, Vigevano F, Bertini E.
Neurogenetics. 2012 Nov;13(4):341-5.
PMID:22949144
PCDH19-related epilepsy in two mosaic male patients.
Terracciano A, Trivisano M, Cusmai R, De Palma L, Fusco L, Compagnucci C, Bertini E, Vigevano F, Specchio N.
Epilepsia. 2016 Mar;57(3):e51-5.
PMID:26765483
Extending the use of stiripentol to other epileptic syndromes: a case of PCDH19-related epilepsy.
Trivisano M, Specchio N, Vigevano F.
Eur J Paediatr Neurol. 2015 Mar;19(2):248-50.
PMID:25510386
Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders.
van Harssel JJ, Weckhuysen S, van Kempen MJ, Hardies K, Verbeek NE, de Kovel CG, Gunning WB, van Daalen E, de Jonge MV, Jansen AC, Vermeulen RJ, Arts WF, Verhelst H, Fogarasi A, de Rijk-van Andel JF, Kelemen A, Lindhout D, De Jonghe P, Koeleman BP, Suls A, Brilstra EH.
Neurogenetics. 2013 Feb;14(1):23-34.
PMID:23334464
Identification of genomic deletions spanning the PCDH19 gene in two unrelated girls with intellectual disability and seizures.
Vincent AK, Noor A, Janson A, Minassian BA, Ayub M, Vincent JB, Morel CF.
Clin Genet. 2012 Dec;82(6):540-5.
PMID:22091964
