Genotype-phenotype correlation in a novel ABHD12 mutation underlying PHARC syndrome.
Charcot-Marie-Tooth disease
Refsum disease
deafness
hereditary neuropathy
retinitis pigmentosa
Journal
Journal of the peripheral nervous system : JPNS
ISSN: 1529-8027
Titre abrégé: J Peripher Nerv Syst
Pays: United States
ID NLM: 9704532
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
26
01
2020
revised:
15
02
2020
accepted:
15
02
2020
pubmed:
23
2
2020
medline:
2
6
2021
entrez:
21
2
2020
Statut:
ppublish
Résumé
PHARC syndrome is a rare neurodegenerative disorder caused by mutations in the ABHD12 gene. It is a genetically heterogeneous and clinically variable disease, which is characterized by demyelinating polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and early-onset cataract and can easily be misdiagnosed as other neurologic disorders with a similar clinical picture, such as Charcot-Marie-Tooth disease and Refsum disease. We describe the genotype-phenotype correlation of two siblings with a novel genotype underlying PHARC syndrome. The genotype was identified using next-generation sequencing. We examined both patients by means of thorough history taking and clinical examination, nerve conduction studies (NCS), brain imaging, and optical coherence tomography to establish a genotype-phenotype correlation. We identified a novel homozygous point mutation (c.784C > T, p.Arg262*) in the ABHD12 gene. This mutation was detected in both siblings, who had bilateral hearing loss and cataracts, signs of cerebellar ataxia, and neuropathy with a primarily demyelinating pattern in NCS. In one case, retinitis pigmentosa was also evident. As PHARC syndrome is a rare autosomal recessive disorder, our findings highlight the importance of an interdisciplinary diagnostic workup with clinical and molecular genetic testing to avoid a misdiagnosis as Charcot-Marie-Tooth disease or Refsum disease.
Substances chimiques
ABHD12 protein, human
EC 3.1.1.23
Monoacylglycerol Lipases
EC 3.1.1.23
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112-116Informations de copyright
© 2020 Peripheral Nerve Society.
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