Predominant neurological phenotype in a Hungarian family with two novel mutations in the XPA gene—case series

Dénes Zádori, László Szpisjak, István Balázs Németh, Zita Reisz, Gabor G. Kovacs, Noémi Szépfalusi, Viola Luca Németh, Zoltán Maróti, Edit Tóth-Molnár, J. Oláh, L. Vécsei, P. Klivényi, Tibor Kalmár

Research output: Contribution to journalArticle

Abstract

Objective: The prevalence of xeroderma pigmentosum (XP) is quite low in Europe, which may result in a delay in determining the appropriate diagnosis. Furthermore, some subtypes of XP, including XPA, may manifest themselves with quite severe neurological symptoms in addition to the characteristic dermatological lesions. Accordingly, the aim of the current study is to highlight the predominant neurological aspects of XPA, as well as mild-to-moderate dermatological signs in a Hungarian family with 5 affected siblings. Case reports: The symptoms of the Caucasian male proband started to develop at 13–14 years of age with predominantly cerebellar, hippocampal, and brainstem alterations. His elder sister and three younger brothers all presented similar, but less expressed neurological signs. The diagnostic work-up, including clinical exome sequencing, revealed 2 novel compound heterozygous mutations (p.Gln146_Tyr148delinsHis, p.Arg258TyrfsTer5) in the XPA gene. Surprisingly, only mild-to-moderate dermatological alterations were observed, and less severe characteristic ophthalmological and auditory signs were detected. Conclusions: In summary, we present the first family with genetically confirmed XPA in the Central-Eastern region of Europe, clearly supporting the notion that disturbed function of the C-terminal region of the XPA protein contributes to the development of age-dependent neurologically predominant signs. This case series may help clinicians recognize this rare disorder.

Original languageEnglish
JournalNeurological Sciences
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Xeroderma Pigmentosum
Exome
Phenotype
Eastern Europe
Mutation
Brain Stem
Genes
Proteins

Keywords

  • Ataxia
  • Cognitive
  • Neurological
  • Neuropathology
  • Parkinsonism
  • Xeroderma pigmentosum group A

ASJC Scopus subject areas

  • Dermatology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Zádori, D., Szpisjak, L., Németh, I. B., Reisz, Z., Kovacs, G. G., Szépfalusi, N., ... Kalmár, T. (Accepted/In press). Predominant neurological phenotype in a Hungarian family with two novel mutations in the XPA gene—case series. Neurological Sciences. https://doi.org/10.1007/s10072-019-04044-6

Predominant neurological phenotype in a Hungarian family with two novel mutations in the XPA gene—case series. / Zádori, Dénes; Szpisjak, László; Németh, István Balázs; Reisz, Zita; Kovacs, Gabor G.; Szépfalusi, Noémi; Németh, Viola Luca; Maróti, Zoltán; Tóth-Molnár, Edit; Oláh, J.; Vécsei, L.; Klivényi, P.; Kalmár, Tibor.

In: Neurological Sciences, 01.01.2019.

Research output: Contribution to journalArticle

Zádori, D, Szpisjak, L, Németh, IB, Reisz, Z, Kovacs, GG, Szépfalusi, N, Németh, VL, Maróti, Z, Tóth-Molnár, E, Oláh, J, Vécsei, L, Klivényi, P & Kalmár, T 2019, 'Predominant neurological phenotype in a Hungarian family with two novel mutations in the XPA gene—case series', Neurological Sciences. https://doi.org/10.1007/s10072-019-04044-6
Zádori, Dénes ; Szpisjak, László ; Németh, István Balázs ; Reisz, Zita ; Kovacs, Gabor G. ; Szépfalusi, Noémi ; Németh, Viola Luca ; Maróti, Zoltán ; Tóth-Molnár, Edit ; Oláh, J. ; Vécsei, L. ; Klivényi, P. ; Kalmár, Tibor. / Predominant neurological phenotype in a Hungarian family with two novel mutations in the XPA gene—case series. In: Neurological Sciences. 2019.
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abstract = "Objective: The prevalence of xeroderma pigmentosum (XP) is quite low in Europe, which may result in a delay in determining the appropriate diagnosis. Furthermore, some subtypes of XP, including XPA, may manifest themselves with quite severe neurological symptoms in addition to the characteristic dermatological lesions. Accordingly, the aim of the current study is to highlight the predominant neurological aspects of XPA, as well as mild-to-moderate dermatological signs in a Hungarian family with 5 affected siblings. Case reports: The symptoms of the Caucasian male proband started to develop at 13–14 years of age with predominantly cerebellar, hippocampal, and brainstem alterations. His elder sister and three younger brothers all presented similar, but less expressed neurological signs. The diagnostic work-up, including clinical exome sequencing, revealed 2 novel compound heterozygous mutations (p.Gln146_Tyr148delinsHis, p.Arg258TyrfsTer5) in the XPA gene. Surprisingly, only mild-to-moderate dermatological alterations were observed, and less severe characteristic ophthalmological and auditory signs were detected. Conclusions: In summary, we present the first family with genetically confirmed XPA in the Central-Eastern region of Europe, clearly supporting the notion that disturbed function of the C-terminal region of the XPA protein contributes to the development of age-dependent neurologically predominant signs. This case series may help clinicians recognize this rare disorder.",
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AU - Reisz, Zita

AU - Kovacs, Gabor G.

AU - Szépfalusi, Noémi

AU - Németh, Viola Luca

AU - Maróti, Zoltán

AU - Tóth-Molnár, Edit

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