, Volume 10, Issue 4, pp 307–311 | Cite as

Neuronal ceroid lipofuscinosis caused by MFSD8 mutations: a common theme emerging

  • M. A. Aldahmesh
  • Z. N. Al-Hassnan
  • M. Aldosari
  • F. S. Alkuraya
Original Article


Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal neurodegenerative disorders that have in common the characteristic accumulation of abnormal storage material. Old clinical classification based on age of onset is now being revisited with the quickly accumulating knowledge of the various genetic defects that underlie this group of genetically heterogeneous disorders. We report our linkage data on a family with late-infantile NCL and show that the disease in this family is due to a homozygous novel mutation in the most recently described NCL gene (MFSD8). We use clinical data from our patients and the few others that have previously been reported to delineate the phenotype associated with mutations in this gene. We conclude that the phenotype is fairly consistent, which is a helpful guide to clinicians as they decide on the most cost-effective molecular testing strategies for NCLs.


Turkish variant Late-infantile NCL Missense Retinitis pigmentosa-like Seizures 


  1. 1.
    Fersht AR (2000) Transition-state structure as a unifying basis in protein-folding mechanisms: contact order, chain topology, stability, and the extended nucleus mechanism. Proc Natl Acad Sci USA 97(4):1525–1529. doi: 10.1073/pnas.97.4.1525 CrossRefPubMedGoogle Scholar
  2. 2.
    Haltia M (2006) The neuronal ceroid-lipofuscinoses: from past to present. Biochim Biophys Acta 1762(10):850–856PubMedGoogle Scholar
  3. 3.
    Lander ES, Botstein D (1987) Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science 236(4808):1567–1570. doi: 10.1126/science.2884728 CrossRefPubMedGoogle Scholar
  4. 4.
    Mole SE (2006) Neuronal ceroid lipofuscinoses (NCL). Eur J Paediatr Neurol 10(5–6):255–257. doi: 10.1016/j.ejpn.2006.08.009 CrossRefPubMedGoogle Scholar
  5. 5.
    Mole SE, Williams RE, Goebel HH (2005) Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. Neurogenetics 6(3):107–126. doi: 10.1007/s10048-005-0218-3 CrossRefPubMedGoogle Scholar
  6. 6.
    Siintola E, Topcu M, Aula N, Lohi H, Minassian BA, Paterson AD, Liu XQ, Wilson C, Lahtinen U, Anttonen AK et al (2007) The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter. Am J Hum Genet 81(1):136–146. doi: 10.1086/518902 CrossRefPubMedGoogle Scholar
  7. 7.
    Stogmann E, El Tawil S, Wagenstaller J, Gaber A, Edris S, Abdelhady A, Assem-Hilger E, Leutmezer F, Bonelli S, Baumgartner C et al (2009) A novel mutation in the MFSD8 gene in late infantile neuronal ceroid lipofuscinosis. Neurogenetics 10(1):73–77. doi: 10.1007/s10048-008-0153-1 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • M. A. Aldahmesh
    • 1
  • Z. N. Al-Hassnan
    • 2
    • 3
  • M. Aldosari
    • 4
  • F. S. Alkuraya
    • 1
    • 3
    • 5
  1. 1.Developmental Genetics Unit, Department of GeneticsKing Faisal Specialist Hospital and Research CenterRiyadhSaudi Arabia
  2. 2.Department of Medical GeneticsKing Faisal Specialist Hospital and Research CenterRiyadhSaudi Arabia
  3. 3.Department of Anatomy and Cell Biology, College of MedicineAlfaisal UniversityRiyadhSaudi Arabia
  4. 4.Department of NeurosciencesKing Faisal Specialist Hospital and Research CenterRiyadhSaudi Arabia
  5. 5.Department of Pediatrics, King Khalid University Hospital and College of MedicineKing Saud UniversityRiyadhSaudi Arabia

Personalised recommendations