title: Impaired cell adhesion and apoptosis in a novel CLN9 Batten disease variant.
abstract: We describe the ninth variant of neuronal ceroid lipofuscinosis (NCL) or Batten disease, due to defects in a putative new gene, CLN9. We therefore refer to the new variant as CLN9-deficient. Two Serbian sisters and two German brothers are described. Their clinical history is characteristic for juvenile NCL. They show similar gene expression patterns. The existence of this variant is supported by the presence of curvilinear inclusions, fingerprint profiles, and granular osmiophilic deposits in neurons, lymphocytes, and conjunctival cells. Enzyme screening and sequencing of the coding regions of other NCL genes was negative. CLN9-deficient cells have a distinctive phenotype. They have rounded cell bodies, have prominent nucleoli, attach poorly to the culture dish, and are sensitive to apoptosis but have increased growth rates. Gene expression of proteins involved in cell adhesion and apoptosis is altered in these cells. Sphingolipid metabolism is also perturbed. They have decreased levels of ceramide, sphingomyelin, lactosylceramide, ceramide trihexoside, and globoside and increased activity of serine palmitoyl transferase.
authors.affiliation: Departments of Pediatrics and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Schulz
authors.forename: Sumeer
authors.initials: S
authors.lastname: Dhar
authors.forename: Svetlana
authors.initials: S
authors.lastname: Rylova
authors.forename: Ghassan
authors.initials: G
authors.lastname: Dbaibo
authors.forename: Joseph
authors.initials: J
authors.lastname: Alroy
authors.forename: Christian
authors.initials: C
authors.lastname: Hagel
authors.forename: Isabelo
authors.initials: I
authors.lastname: Artacho
authors.forename: Alfried
authors.initials: A
authors.lastname: Kohlschütter
authors.forename: Simon
authors.initials: S
authors.lastname: Lin
authors.forename: Rose-Mary
authors.initials: RM
authors.lastname: Boustany
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D008565:Membrane Proteins