title: Truncating mutation in intracellular phospholipase A₁ gene (DDHD2) in hereditary spastic paraplegia with intellectual disability (SPG54).
abstract: BACKGROUND
  Hereditary spastic paraplegias (HSP), a group of genetically heterogeneous neurological disorders with more than 56 documented loci (SPG1-56), are described either as uncomplicated (or pure), or complicated where in addition to spasticity and weakness of lower extremeties, additional neurological symptoms are present, including dementia, loss of vision, epilepsy, mental retardation and ichthyosis. We identified a large consanguineous family of Indian descent with four affected members with childhood onset HSP (SPG54), presenting with upper and lower limb spasticity, mental retardation and agenesis of the corpus callosum.
  
  
  RESULTS
  A common region of homozygosity on chromosome 8 spanning seven megabases (Mb) was identified in the affected individuals using the Illumina human cytoSNP-12 DNA Analysis BeadChip Kit. Exome sequencing identified a homozygous stop gain mutation (pR287X) in the phospholipase A1 gene DDHD2, in the affected individuals, resulting in a premature stop codon and a severely truncated protein lacking the SAM and DDHD domains crucial for phosphoinositide binding and phospholipase activity.
  
  
  CONCLUSIONS
  This mutation adds to the knowledge of HSP, suggests a possible founder effect for the pR287X mutation, and adds to the list of genes involved in lipid metabolism with a role in HSP and other neurodegenerative disorders.
authors.affiliation: Princess Al-Jawhara Albrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, 80205, Kingdom of Saudi Arabia. nuharayes@gmail.com.|Division of Biomedical Sciences (BMS), Human Genetics Research Center, St. George's University of London (SGUL), London, SW17 0RE, UK. nuharayes@gmail.com.
authors.forename: Nuha
authors.initials: N
authors.lastname: Alrayes
authors.affiliation: Princess Al-Jawhara Albrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, 80205, Kingdom of Saudi Arabia. husseinsheekh@yahoo.co.uk.|Division of Biomedical Sciences (BMS), Human Genetics Research Center, St. George's University of London (SGUL), London, SW17 0RE, UK. husseinsheekh@yahoo.co.uk.
authors.forename: Hussein Sheikh Ali
authors.initials: HS
authors.lastname: Mohamoud
authors.affiliation: Princess Al-Jawhara Albrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, 80205, Kingdom of Saudi Arabia. musharraf_jelani@yahoo.com.|Medical Genetics and Molecular Biology Unit, Biochemistry Department, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, 25000, Pakistan. musharraf_jelani@yahoo.com.
authors.forename: Musharraf
authors.initials: M
authors.lastname: Jelani
authors.affiliation: Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. sahmad@yahoo.com.
authors.forename: Saleem
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Division of Biomedical Sciences (BMS), Human Genetics Research Center, St. George's University of London (SGUL), London, SW17 0RE, UK. nvadgama@sgul.ac.uk.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Vadgama
authors.affiliation: Princess Al-Jawhara Albrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, 80205, Kingdom of Saudi Arabia. kbakur@yahoo.com.
authors.forename: Khadijah
authors.initials: K
authors.lastname: Bakur
authors.affiliation: Genetics and Molecular Medicine, King's College London, Guy's Hospital, London, SE1 9RT, UK. michael.simpson@kcl.ac.uk.
authors.forename: Michael
authors.initials: M
authors.lastname: Simpson
authors.affiliation: Princess Al-Jawhara Albrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, 80205, Kingdom of Saudi Arabia. al-aama@yahoo.com.|Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. al-aama@yahoo.com.
authors.forename: Jumana Yousuf
authors.initials: JY
authors.lastname: Al-Aama
authors.affiliation: Division of Biomedical Sciences (BMS), Human Genetics Research Center, St. George's University of London (SGUL), London, SW17 0RE, UK. p1106394@sgul.ac.uk.
authors.forename: Jamal
authors.initials: J
authors.lastname: Nasir
mesh_terms: D061085:Agenesis of Corpus Callosum / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D001842:Bone and Bones / Q000002:abnormalities* / Q000473:pathology; D002675:Child, Preschool; D002898:Chromosomes, Human, Pair 8; D018389:Codon, Nonsense; D003241:Consanguinity; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010740:Phospholipases / Q000235:genetics*; D017434:Protein Structure, Tertiary; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology
chemical_list: D018389:Codon, Nonsense; D010740:Phospholipases; C541017:DDHD2 protein, human