Genetic and phenotypic variability in adult patients with Niemann Pick type C from Serbia: single-center experience

Autor: Nikola Kresojević, Valerija Dobričić, Milica Ječmenica Lukić, Aleksandra Tomić, Igor Petrović, Nataša Dragašević, Ivana Perović, Ana Marjanović, Marija Branković, Milena Janković, Ivana Novaković, Marina Svetel, Vladimir S. Kostić
Rok vydání: 2022
Předmět:
Zdroj: Journal of Neurology. 269:3167-3174
ISSN: 1432-1459
0340-5354
2012-2020
Popis: Niemann Pick type C is an autosomal recessive lysosomal storage disorder caused by mutations in NPC1 and NPC2 genes. It is a neuro-visceral disease with a heterogeneous phenotype. Clinical features depend on the age at onset. Visceral manifestations are more prominent in the early onset (infantile) form, while neuro-psychiatric symptoms are more prominent in the late disease onset (juvenile and adult forms).A total number of 150 patients have been screened for changes in NPC1 and NPC2 gene at the Neurology Clinic, University Clinical Centre of Serbia in the period 2012-2020. Clinical data were extracted for patients with biallelic mutations.Fifteen patients carried biallelic mutations in the NPC1. Out of eight different reported NPC1 variants, four are novel (c.1204_1205TTGC, p.F402A; c.2486TG, p.L829R; c.2795+5 GC; c.3722TA, p.L1241*). The mean age at the disease onset was 20.3 ± 11.9 years with the average diagnostic delay of 7.7 ± 4.3 years. Movement disorders and psychiatric or cognitive disturbances were the most common initial symptoms (in 33% and 28% patients, respectively). The average age at the first neurological manifestation was 21 ± 12.0 years. At the last examination, eye movement abnormalities (vertical slow saccades or vertical supranuclear gaze palsy), and ataxia were present in all patients, while dystonia was common (in 78.6% of patients). Presence of c.2861CT, p.S954L mutation in homozygous state was associated with older age at the neurological symptom onset.Clinical findings were in line with the expected, but the diagnostic delay was common. We hypothesize that the presence of c.2861CT, p.S954L mutation may contribute to the phenotype attenuation.
Databáze: OpenAIRE
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