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1.  De novo mutations in ATP1A3 cause alternating hemiplegia of childhood 
Heinzen, Erin L. | Swoboda, Kathryn J. | Hitomi, Yuki | Gurrieri, Fiorella | Nicole, Sophie | de Vries, Boukje | Tiziano, F. Danilo | Fontaine, Bertrand | Walley, Nicole M. | Heavin, Sinéad | Panagiotakaki, Eleni | Fiori, Stefania | Abiusi, Emanuela | Di Pietro, Lorena | Sweney, Matthew T. | Newcomb, Tara M. | Viollet, Louis | Huff, Chad | Jorde, Lynn B. | Reyna, Sandra P. | Murphy, Kelley J. | Shianna, Kevin V. | Gumbs, Curtis E. | Little, Latasha | Silver, Kenneth | Ptác̆ek, Louis J. | Haan, Joost | Ferrari, Michel D. | Bye, Ann M. | Herkes, Geoffrey K. | Whitelaw, Charlotte M. | Webb, David | Lynch, Bryan J. | Uldall, Peter | King, Mary D. | Scheffer, Ingrid E. | Neri, Giovanni | Arzimanoglou, Alexis | van den Maagdenberg, Arn M.J.M. | Sisodiya, Sanjay M. | Mikati, Mohamad A. | Goldstein, David B. | Nicole, Sophie | Gurrieri, Fiorella | Neri, Giovanni | de Vries, Boukje | Koelewijn, Stephany | Kamphorst, Jessica | Geilenkirchen, Marije | Pelzer, Nadine | Laan, Laura | Haan, Joost | Ferrari, Michel | van den Maagdenberg, Arn | Zucca, Claudio | Bassi, Maria Teresa | Franchini, Filippo | Vavassori, Rosaria | Giannotta, Melania | Gobbi, Giuseppe | Granata, Tiziana | Nardocci, Nardo | De Grandis, Elisa | Veneselli, Edvige | Stagnaro, Michela | Gurrieri, Fiorella | Neri, Giovanni | Vigevano, Federico | Panagiotakaki, Eleni | Oechsler, Claudia | Arzimanoglou, Alexis | Nicole, Sophie | Giannotta, Melania | Gobbi, Giuseppe | Ninan, Miriam | Neville, Brian | Ebinger, Friedrich | Fons, Carmen | Campistol, Jaume | Kemlink, David | Nevsimalova, Sona | Laan, Laura | Peeters-Scholte, Cacha | van den Maagdenberg, Arn | Casaer, Paul | Casari, Giorgio | Sange, Guenter | Spiel, Georg | Boneschi, Filippo Martinelli | Zucca, Claudio | Bassi, Maria Teresa | Schyns, Tsveta | Crawley, Francis | Poncelin, Dominique | Vavassori, Rosaria
Nature genetics  2012;44(9):1030-1034.
Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurologic manifestations. AHC is usually a sporadic disorder with unknown etiology. Using exome sequencing of seven patients with AHC, and their unaffected parents, we identified de novo nonsynonymous mutations in ATP1A3 in all seven AHC patients. Subsequent sequence analysis of ATP1A3 in 98 additional patients revealed that 78% of AHC cases have a likely causal ATP1A3 mutation, including one inherited mutation in a familial case of AHC. Remarkably, six ATP1A3 mutations explain the majority of patients, including one observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset-dystonia-parkinsonism, AHC-causing mutations revealed consistent reductions in ATPase activity without effects on protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC, and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in this gene.
doi:10.1038/ng.2358
PMCID: PMC3442240  PMID: 22842232
2.  Identification of a rare 17p13.3 duplication including the BHLHA9 and YWHAE genes in a family with developmental delay and behavioural problems 
BMC Medical Genetics  2012;13:93.
Background
Deletions and duplications of the PAFAH1B1 and YWHAE genes in 17p13.3 are associated with different clinical phenotypes. In particular, deletion of PAFAH1B1 causes isolated lissencephaly while deletions involving both PAFAH1B1 and YWHAE cause Miller-Dieker syndrome. Isolated duplications of PAFAH1B1 have been associated with mild developmental delay and hypotonia, while isolated duplications of YWHAE have been associated with autism. In particular, different dysmorphic features associated with PAFAH1B1 or YWHAE duplication have suggested the need to classify the patient clinical features in two groups according to which gene is involved in the chromosomal duplication.
Methods
We analyze the proband and his family by classical cytogenetic and array-CGH analyses. The putative rearrangement was confirmed by fluorescence in situ hybridization.
Results
We have identified a family segregating a 17p13.3 duplication extending 329.5 kilobases by FISH and array-CGH involving the YWHAE gene, but not PAFAH1B1, affected by a mild dysmorphic phenotype with associated autism and mental retardation. We propose that BHLHA9, YWHAE, and CRK genes contribute to the phenotype of our patient. The small chromosomal duplication was inherited from his mother who was affected by a bipolar and borderline disorder and was alcohol addicted.
Conclusions
We report an additional familial case of small 17p13.3 chromosomal duplication including only BHLHA9, YWHAE, and CRK genes. Our observation and further cases with similar microduplications are expected to be diagnosed, and will help better characterise the clinical spectrum of phenotypes associated with 17p13.3 microduplications.
doi:10.1186/1471-2350-13-93
PMCID: PMC3495055  PMID: 23035971
Familial 17p13.3 duplication syndrome; PAFAH1B1 and YWHAE genes; Array-CGH

Results 1-2 (2)