Late Infantile Metachromatic Leukodystrophy Due to Novel Pathogenic Variants in the PSAP Gene.

Abstract

Impairment of saposin B causes rare atypical metachromatic leukodystrophy (MLD). It is encoded (together with saposin A, C, and D) by the PSAP gene. Only ten pathogenic variants were described in the PSAP gene in MLD patients to date. We report on two novel variants in the PSAP gene - c.679_681delAAG in the saposin B encoding exon 6 and c.1268delT in the saposin D encoding exon 11 in a patient with MLD. We discuss the fact, that variants resulting in PSAP null allele can be shared in patients with the deficit of other saposins (A-D) or whole prosaposin. The patient's phenotype depends then on the nature of the second allele - atypical Gaucher disease in case of saposin A, MLD in case of saposin B, and Krabbe disease in case of saposin C impairing mutations. The clinically most severe prosaposin deficit is caused by the presence of two PSAP null alleles. Thus, the assessment of a variant impact is needed to prevent delayed diagnosis or misdiagnosis in patients with PSAP mutations.

• Authors: Miriam Kolnikova, Petra Jungova, Martina Skopkova, Tomas Foltan, Daniela Gasperikova, Slavomira Mattosova, Jan Chandoga
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 67 Issue 4 Pg. 559-563 (Apr 2019) ISSN: 1559-1166 [Electronic] United States
• PMID: 30632081 (Publication Type: Case Reports, Journal Article)

Chemical References

• PSAP protein, human
• Saposins

Topics

• Exons
• Humans
• Infant
• Leukodystrophy, Metachromatic (genetics, pathology)
• Loss of Function Mutation
• Male
• Phenotype
• Saposins (genetics)