Case Report: Identification of a Heterozygous XPA c.553C>T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group A
We aimed to determine if an adolescent patient presenting with neurological impairment has xeroderma pigmentosum (XP). For this purpose, whole-exome sequencing was performed to assess mutations in XP genes. Dermal fibroblasts were established from a skin biopsy and XPA expression determined by immun...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-08-01
|
Series: | Frontiers in Genetics |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.717361/full |
id |
doaj-f121378d117e43b6b460fd98cf5559d3 |
---|---|
record_format |
Article |
spelling |
doaj-f121378d117e43b6b460fd98cf5559d32021-08-16T07:06:12ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-08-011210.3389/fgene.2021.717361717361Case Report: Identification of a Heterozygous XPA c.553C>T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group AJuan Antonio García-Carmona0Matthew J. Yousefzadeh1Fernando Alarcón-Soldevilla2Eva Fages-Caravaca3Eva Fages-Caravaca4Tra L. Kieu5Mariah A. Witt6Ángel López-Ávila7Laura J. Niedernhofer8José Antonio Pérez-Vicente9Department of Neurology, Santa Lucia University Hospital, Cartagena, SpainDepartment of Biochemistry, Molecular Biology, and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, United StatesDepartment of Dermatology, Santa María del Rosell University Hospital, Cartagena, SpainDepartment of Neurology, Santa Lucia University Hospital, Cartagena, SpainUnit of Neuromuscular Disorders, Santa Lucia University Hospital, Cartagena, SpainDepartment of Biochemistry, Molecular Biology, and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, United StatesDepartment of Biochemistry, Molecular Biology, and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, United StatesDepartment of Dermatology, Santa María del Rosell University Hospital, Cartagena, SpainDepartment of Biochemistry, Molecular Biology, and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, United StatesDepartment of Neurology, Santa Lucia University Hospital, Cartagena, SpainWe aimed to determine if an adolescent patient presenting with neurological impairment has xeroderma pigmentosum (XP). For this purpose, whole-exome sequencing was performed to assess mutations in XP genes. Dermal fibroblasts were established from a skin biopsy and XPA expression determined by immunoblotting. Nucleotide excision repair (NER) capacity was measured by detection of unscheduled DNA synthesis (UDS) in UVC-irradiated patient fibroblasts. Genetic analysis revealed two recessive mutations in XPA, one known c.682C>T, p.Arg228Ter, and the other c.553C>T, p.Gln185Ter, only two cases were reported. XPA protein was virtually undetectable in lysates from patient-derived fibroblast. The patient had significantly lower UV-induced UDS (3.03 ± 1.95%, p < 0.0001) compared with healthy controls (C5RO = 100 ± 12.2; C1UMN = 118 ± 5.87), indicating significant NER impairment. In conclusion, measurement of NER capacity is beneficial for the diagnosis of XP and in understanding the functional impact of novel mutations in XP genes. Our findings highlight the importance of neurologists considering XP in their differential diagnosis when evaluating patients with atypical neurodegeneration.https://www.frontiersin.org/articles/10.3389/fgene.2021.717361/fullxeroderma pigmentosum group Aneurode generationDNA repair activitynucleotide excision repairmutationrare diseases |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Juan Antonio García-Carmona Matthew J. Yousefzadeh Fernando Alarcón-Soldevilla Eva Fages-Caravaca Eva Fages-Caravaca Tra L. Kieu Mariah A. Witt Ángel López-Ávila Laura J. Niedernhofer José Antonio Pérez-Vicente |
spellingShingle |
Juan Antonio García-Carmona Matthew J. Yousefzadeh Fernando Alarcón-Soldevilla Eva Fages-Caravaca Eva Fages-Caravaca Tra L. Kieu Mariah A. Witt Ángel López-Ávila Laura J. Niedernhofer José Antonio Pérez-Vicente Case Report: Identification of a Heterozygous XPA c.553C>T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group A Frontiers in Genetics xeroderma pigmentosum group A neurode generation DNA repair activity nucleotide excision repair mutation rare diseases |
author_facet |
Juan Antonio García-Carmona Matthew J. Yousefzadeh Fernando Alarcón-Soldevilla Eva Fages-Caravaca Eva Fages-Caravaca Tra L. Kieu Mariah A. Witt Ángel López-Ávila Laura J. Niedernhofer José Antonio Pérez-Vicente |
author_sort |
Juan Antonio García-Carmona |
title |
Case Report: Identification of a Heterozygous XPA c.553C>T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group A |
title_short |
Case Report: Identification of a Heterozygous XPA c.553C>T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group A |
title_full |
Case Report: Identification of a Heterozygous XPA c.553C>T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group A |
title_fullStr |
Case Report: Identification of a Heterozygous XPA c.553C>T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group A |
title_full_unstemmed |
Case Report: Identification of a Heterozygous XPA c.553C>T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group A |
title_sort |
case report: identification of a heterozygous xpa c.553c>t mutation causing neurological impairment in a case of xeroderma pigmentosum complementation group a |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2021-08-01 |
description |
We aimed to determine if an adolescent patient presenting with neurological impairment has xeroderma pigmentosum (XP). For this purpose, whole-exome sequencing was performed to assess mutations in XP genes. Dermal fibroblasts were established from a skin biopsy and XPA expression determined by immunoblotting. Nucleotide excision repair (NER) capacity was measured by detection of unscheduled DNA synthesis (UDS) in UVC-irradiated patient fibroblasts. Genetic analysis revealed two recessive mutations in XPA, one known c.682C>T, p.Arg228Ter, and the other c.553C>T, p.Gln185Ter, only two cases were reported. XPA protein was virtually undetectable in lysates from patient-derived fibroblast. The patient had significantly lower UV-induced UDS (3.03 ± 1.95%, p < 0.0001) compared with healthy controls (C5RO = 100 ± 12.2; C1UMN = 118 ± 5.87), indicating significant NER impairment. In conclusion, measurement of NER capacity is beneficial for the diagnosis of XP and in understanding the functional impact of novel mutations in XP genes. Our findings highlight the importance of neurologists considering XP in their differential diagnosis when evaluating patients with atypical neurodegeneration. |
topic |
xeroderma pigmentosum group A neurode generation DNA repair activity nucleotide excision repair mutation rare diseases |
url |
https://www.frontiersin.org/articles/10.3389/fgene.2021.717361/full |
work_keys_str_mv |
AT juanantoniogarciacarmona casereportidentificationofaheterozygousxpac553ctmutationcausingneurologicalimpairmentinacaseofxerodermapigmentosumcomplementationgroupa AT matthewjyousefzadeh casereportidentificationofaheterozygousxpac553ctmutationcausingneurologicalimpairmentinacaseofxerodermapigmentosumcomplementationgroupa AT fernandoalarconsoldevilla casereportidentificationofaheterozygousxpac553ctmutationcausingneurologicalimpairmentinacaseofxerodermapigmentosumcomplementationgroupa AT evafagescaravaca casereportidentificationofaheterozygousxpac553ctmutationcausingneurologicalimpairmentinacaseofxerodermapigmentosumcomplementationgroupa AT evafagescaravaca casereportidentificationofaheterozygousxpac553ctmutationcausingneurologicalimpairmentinacaseofxerodermapigmentosumcomplementationgroupa AT tralkieu casereportidentificationofaheterozygousxpac553ctmutationcausingneurologicalimpairmentinacaseofxerodermapigmentosumcomplementationgroupa AT mariahawitt casereportidentificationofaheterozygousxpac553ctmutationcausingneurologicalimpairmentinacaseofxerodermapigmentosumcomplementationgroupa AT angellopezavila casereportidentificationofaheterozygousxpac553ctmutationcausingneurologicalimpairmentinacaseofxerodermapigmentosumcomplementationgroupa AT laurajniedernhofer casereportidentificationofaheterozygousxpac553ctmutationcausingneurologicalimpairmentinacaseofxerodermapigmentosumcomplementationgroupa AT joseantonioperezvicente casereportidentificationofaheterozygousxpac553ctmutationcausingneurologicalimpairmentinacaseofxerodermapigmentosumcomplementationgroupa |
_version_ |
1721206047829393408 |