Novel mutation and the first prenatal screening of cathepsin D deficiency (CLN10)
| Autor: | Cynthia M. Powell, Anna-Elina Lehesjoki, Jaana Tyynelä, Sabine Koch, Jessica M. Booker, Michael B. Tennison, Karen J. Fritchie, Diane Armao, Thomas Marino, Kinuko Suzuki, Leigh B. Thorne, Sanna Partanen, Eija Siintola |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Sphingolipid Activator Proteins medicine.medical_specialty Microcephaly Pathology Cathepsin D Prenatal diagnosis Biology Pathology and Forensic Medicine Cellular and Molecular Neuroscience Exon Neuronal Ceroid-Lipofuscinoses Pregnancy Internal medicine Muscle Hypertonia medicine Lysosomal storage disease Humans Point Mutation Gliosis Brain Chemistry Neurons Cell Death Macrophages Infant Newborn Brain Fibroblasts medicine.disease Hypoplasia Endocrinology Chorionic Villi Sampling Astrocytes Female Neuronal ceroid lipofuscinosis Neurology (clinical) medicine.symptom |
| Zdroj: | Acta Neuropathologica. 117:201-208 |
| ISSN: | 1432-0533 0001-6322 |
| DOI: | 10.1007/s00401-008-0426-7 |
| Popis: | The neuronal ceroid lipofuscinoses (NCLs) are autosomal recessively inherited disorders collectively considered to be one among the most common pediatric neurodegenerative lysosomal storage diseases. Four main clinical subtypes have been described based on the age at presentation: infantile, late infantile, juvenile and adult types. In addition, rare congenital cases of NCL have been reported in the literature. Previously, a homozygous mutation in the cathepsin D gene has been shown to cause congenital NCL in a patient of Pakistani origin. We report a case of a 39-week estimated gestational age female infant with severe microcephaly and hypertonia, whereas MRI showed generalized hypoplasia of the cerebral and cerebellar hemispheres. The infant died on day two after birth. Postmortem examination revealed a small, firm brain with extensive neuronal loss and gliosis. Remaining neurons, astrocytes and macrophages contained PAS-positive storage material with granular ultrastructure and immunoreactivity against sphingolipid activator protein D. A diagnosis of congenital NCL was rendered with a novel mutation, c.299C > T (p.Ser100Phe) in exon 3 of the cathepsin D gene. In the patient fibroblasts, cathepsin D activity was marginal, but the protein appeared stable and normally processed. This was confirmed in overexpression studies. Importantly, by identification of the mutation in the family, we were able to confirm the first prenatal diagnosis excluding cathepsin D deficiency in the younger sibling of the patient. |
| Databáze: | OpenAIRE |
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