Prenatal diagnosis of variant late infantile neuronal ceroid lipofuscinosis (vLINCL[Finnish]; CLN5).
The first prenatal diagnosis of variant late infantile neuronal ceroid lipofuscinosis (vLINCL[Finnish]; CLN5) is reported. The disease belongs to the group of progressive encephalopathies in children with psycho-motor deterioration, visual failure and premature death. Neurons and several extraneural cells harbour lysosomal inclusions showing accumulation of material with histochemical characteristics of ceroid and lipofuscin. A Finnish woman with a daughter with vLINCL came for genetic counselling for her current pregnancy. Electron microscopy of a chorionic villus sample (CVS) at the 11th week of gestation did not reveal inclusions characteristic for NCL. DNA analysis showed that the fetus had inherited the major mutation, a 2 bp deletion of the CLN5 gene from the mother, and the same paternal (and maternal) haplotypes for COLAC1 and AC224 as the affected daughter. The pregnancy was terminated. Electron microscopy of the CVS of the aborted fetus at the 14th week of pregnancy showed lysosomal electron dense inclusions with straight and curved lamellar profiles consistent with vLINCL. Prenatal diagnosis of NCL-disorders (CLN1, CLN2, CLN3) can be made from CVS by demonstrating the mutations of the affected genes or by haplotype analysis using the closely linked markers in most cases. In various clinical settings the DNA diagnostics may not be possible. Demonstration of the characteristic inclusions of the placenta and fetal tissues remains a helpful adjunct in such cases.
Haartman Institute, Department of Pathology, University of Helsinki, Haartmaninkatu 3, 00290 Helsinki, Finland.
J
J
Rapola
J
J
Lähdetie
J
J
Isosomppi
P
P
Helminen
M
M
Penttinen
I
I
Järvelä
D002648:Child; D015193:Chorionic Villi Sampling; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D005865:Gestational Age; D006239:Haplotypes; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins / Q000235:genetics; D008854:Microscopy, Electron; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011247:Pregnancy; D011296:Prenatal Diagnosis; D000091346:Tripeptidyl-Peptidase 1
C113332:CLN5 protein, human; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D000091346:Tripeptidyl-Peptidase 1; C000717267:TPP1 protein, human