Identification of a TPP1 Q278X Mutation in an Iranian Patient with Neuronal Ceroid Lipofuscinosis 2: Literature Review and Mutations Update

Tayebeh Baranzehi; Dor Mohammad Kordi-Tamandani; Maryam Najafi; Ali Khajeh; Miriam Schmidts

doi:10.3390/jcm11216415

Identification of a TPP1 Q278X Mutation in an Iranian Patient with Neuronal Ceroid Lipofuscinosis 2: Literature Review and Mutations Update

J Clin Med. 2022 Oct 29;11(21):6415. doi: 10.3390/jcm11216415.

Authors

Tayebeh Baranzehi¹, Dor Mohammad Kordi-Tamandani¹, Maryam Najafi^{2

3}, Ali Khajeh⁴, Miriam Schmidts^{2

3

5}

Affiliations

¹ Departement of Biology, University of Sistan and Baluchestan, Zahedan 9816745845, Iran.
² Pediatric Genetics Division, Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg University Faculty of Medicine, 79106 Freiburg, Germany.
³ Genome Research Division, Human Genetics Department, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
⁴ Department of Pediatric, Children and Adolescent Health Research Center, Zahedan University of Medical Sciences, Zahedan 9816745845, Iran.
⁵ CIBSS-Center for Integrative Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany.

Abstract

Neuronal ceroid lipofuscinoses type 2 (CLN2), the most common form of Batten disease, is caused by TPP1 loss of function, resulting in tripeptidyl peptidase-1 enzyme deficiency and cerebral accumulation of lipopigments. Clinical hallmarks include epileptic seizures, vision loss, progressive movement disorder, ataxia, and eventually death. Diagnosis is often delayed due to the rarity of the conditions. Results: Here, we report a case presenting with clinical features of CLN2, carrying a homozygous novel nonsense variant in TPP1 (NM_000391:c.C832T, (p.Q278*), rs1352347549). Moreover, we performed a comprehensive literature review regarding previously identified disease-causing TPP1 mutations and genotype-phenotype correlations. Conclusion: Depending on the type of mutation, different phenotypes are observed in patients with CLN2, suggesting that the severity of phenotypes is related to the genotype of the patients.

Keywords: CLN2; R278*; TPP1 gene; c.C832T.

Abstract

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