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

• Published in: Neurological sciences 2020-01, Vol.41 (1), p.125-129
• Main Authors: Zádori, Dénes, Szpisjak, László, Németh, István Balázs, Reisz, Zita, Kovacs, Gabor G., Szépfalusi, Noémi, Németh, Viola Luca, Maróti, Zoltán, Tóth-Molnár, Edit, Oláh, Judit, Vécsei, László, Klivényi, Péter, Kalmár, Tibor
• Format: Article
• Language: English
• Subjects: Age; Brain diseases; Brain stem; Case reports; Cerebellum; Hippocampus; Medicine; Medicine & Public Health; Mutation; Neurology; Neuroradiology; Neurosciences; Neurosurgery; Original; Original Article; Phenotypes; Psychiatry; Xeroderma pigmentosum; XPA protein
• ISSN: 1590-1874; 1590-3478
• DOI: 10.1007/s10072-019-04044-6

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.