Browsing by Author "Emma L. Baple"

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A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations
(BioMed Central Ltd., 2015) Thomas Iype; Vafa Alakbarzade; Mary Iype; Royana Singh; Ajith Sreekantan-Nair; Barry A. Chioza; Tribhuvan M. Mohapatra; Emma L. Baple; Michael A. Patton; Thomas T. Warner; Christos Proukakis; Abhi Kulkarni; Andrew H. Crosby
Background: The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance. Methods and results: We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features. Conclusion: We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals. © 2015 Iype et al.
Copy number variation of LINGO1 in familial dystonic tremor
(Lippincott Williams and Wilkins, 2019) Vafa Alakbarzade; Thomas Iype; Barry A. Chioza; Royana Singh; Gaurav V. Harlalka; Holly Hardy; Ajith Sreekantan-Nair; Christos Proukakis; Kathryn Peall; Lorraine N. Clark; Richard Caswell; Hana Lango Allen; Matthew Wakeling; John K. Chilton; Emma L. Baple; Elan D. Louis; Thomas T. Warner; Andrew H. Crosby
Objective To elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor. Methods Whole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals. Results Whole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members. Whole-genome sequencing demonstrated that it comprised a ∼550-kb tandem duplication encompassing the entire LINGO1 gene. Conclusions The identification of a genomic duplication as the likely molecular cause of this condition, resulting in an additional LINGO1 gene copy in affected cases, adds further support for a causal role of this gene in tremor disorders and implicates increased expression levels of LINGO1 as a potential pathogenic mechanism. © American Academy of Neurology.
PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment
(Oxford University Press, 2017) Massimo Zollo; Mustafa Ahmed; Veronica Ferrucci; Vincenzo Salpietro; Fatemeh Asadzadeh; Marianeve Carotenuto; Reza Maroofian; Ahmed Al-Amri; Royana Singh; Iolanda Scognamiglio; Majid Mojarrad; Luca Musella; Angela Duilio; Angela Di Somma; Ender Karaca; Anna Rajab; Aisha Al-Khayat; Tribhuvan Mohan Mohapatra; Atieh Eslahi; Farah Ashrafzadeh; Lettie E. Rawlins; Rajniti Prasad; Rashmi Gupta; Preeti Kumari; Mona Srivastava; Flora Cozzolino; Sunil Kumar Rai; Maria Monti; Gaurav V. Harlalka; Michael A. Simpson; Philip Rich; Fatema Al-Salmi; Michael A. Patton; Barry A. Chioza; Stephanie Efthymiou; Francesca Granata; Gabriella Di Rosa; Sarah Wiethoff; Eugenia Borgione; Carmela Scuderi; Kshitij Mankad; Michael G. Hanna; Piero Pucci; Henry Houlden; James R. Lupski; Andrew H. Crosby; Emma L. Baple
PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation. © The Author (2017).