title: Clinical and genetic studies in patients with Lafora disease from Pakistan.
abstract: Lafora disease (LD) is progressive myoclonic epilepsy with late childhood- to teenage-onset. Mutations in two genes, EPM2A and NHLRC1, are responsible for this autosomal recessive disease in many patients Worldwide. In present study, we reported two unrelated consanguineous Pakistani families with Lafora disease (Families A and B). Affected individuals in both families presented with generalized tonic clonic seizures, intellectual disability, ataxia and cognitive decline. Diagnosis of Lafora disease was made on histo-pathological analysis of the skin biopsy, found positive for lafora bodies in periodic acid schiff stain and frequent generalized epileptiform discharges on electroencephalogram (EEG). Bi-directional sequencing in family A was performed for EPM2A and NHLRC1 genes but no mutation was found. In family B, Illumina TruSight One Sequencing Panel covering 4813 OMIM genes was carried out and we identified a novel homozygous mutation c.95G>T; p.32Trp>Leu of EPM2A gene which was found co-segregated in this family through Sanger sequencing. Structural analysis of this mutation, through different in silico approaches, predicted loss of stability and conformation in Laforin protein.
authors.affiliation: Division of Neurology, Shifa International Hospital, Shifa Tameer e Millat University, Islamabad, Pakistan.
authors.forename: Arsalan
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences & Technology (NUST), Islamabad, Pakistan.
authors.forename: Rubina
authors.initials: R
authors.lastname: Dad
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad Ikram
authors.initials: MI
authors.lastname: Ullah
authors.affiliation: Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences & Technology (NUST), Islamabad, Pakistan.
authors.forename: Tahir Ahmed
authors.initials: TA
authors.lastname: Baig
authors.affiliation: Division of Pathology, Shifa International Hospital, Shifa Tameer e Millat University, Islamabad, Pakistan.
authors.forename: Imran N
authors.initials: IN
authors.lastname: Ahmad
authors.affiliation: Department of Biochemistry, Abdul Wali Khan University Mardan, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Nasir
authors.affiliation: Institute of Human Genetics, University of Jena, Kollegiengasse 10, D-07743 Jena, Germany.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hübner
authors.affiliation: Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences & Technology (NUST), Islamabad, Pakistan. Electronic address: mjh@asab.nust.edu.pk.
authors.forename: Muhammad Jawad
authors.initials: MJ
authors.lastname: Hassan
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D020192:Lafora Disease / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D010154:Pakistan; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000473:pathology; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; C478960:NHLRC1 protein, human; D044767:Ubiquitin-Protein Ligases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human
keywords: EPM2A; Lafora disease; Mutation; Pakistani families