Phenotypical features of two patients diagnosed with PHARC syndrome and carriers of a new homozygous mutation in the ABHD12 gene

@article{Frasquet2018PhenotypicalFO,
  title={Phenotypical features of two patients diagnosed with PHARC syndrome and carriers of a new homozygous mutation in the ABHD12 gene},
  author={Marina Frasquet and Vincenzo Lupo and Mar{\'i}a Jos{\'e} Chumillas and Juan Francisco V{\'a}zquez-Costa and Carmen Espin{\'o}s and Teresa Sevilla},
  journal={Journal of the Neurological Sciences},
  year={2018},
  volume={387},
  pages={134-138}
}
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10 Citations
Background Citations
2
Results Citations
2

10 Citations

Genotype‐phenotype correlation in a novel ABHD12 mutation underlying PHARC syndrome
TLDR
The genotype‐phenotype correlation of two siblings with a novel genotype underlying PHARC syndrome is described, which highlights 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.
PHARC Syndrome, a Rare Genetic Disorder—Case Report
TLDR
The first case of a Portuguese PHARC patient is presented, highlighting how despite the presence of typical symptoms earlier diagnosis was precluded due to its rarity.
The Phenotypic Spectrum of Patients with PHARC Syndrome Due to Variants in ABHD12: An Ophthalmic Perspective
TLDR
From an ophthalmic perspective, clinical manifestations in patients with PHARC demonstrate variability with regard to their onset and severity, and an early multidisciplinary assessment is recommended to assess disease severity.
A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review.
Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome
TLDR
Three children with hearing and vision loss with clinical and genetic findings suggestive of Usher syndrome are presented, but ongoing clinical assessment did not completely support an USH diagnosis, and exome analysis was pursued for all three individuals.
Atypical and ultra-rare Usher syndrome: a review
TLDR
The molecular etiology of Usher syndrome is reviewed, highlighting rare presentations and molecular causes, and guidelines for establishing a clear nomenclature system are suggested.
Dark-adapted threshold and electroretinogram for diagnosis of Usher syndrome
TLDR
Although there is an association of abnormal dark-adapted threshold and full-field electroretinogram at young ages in Usher patients, it appears that a small but important proportion of patients would not be detected by tests of retinal function alone.
Mapping the neuroanatomy of ABHD16A-ABHD12 & lysophosphatidylserines provides new insights into the pathophysiology of the human neurological disorder PHARC.
TLDR
Using subcellular organelle fractionation, biochemical assays and immunofluorescence based high resolution microscopy, the PS lipase ABHD16A is an endoplasmic reticulum (ER) localized enzyme, an organelle intricately regulating cellular PS levels, providing new insights into lyso-PS signaling in the cerebellum, the most atrophic brain region in human PHARC subjects.
Druggable Targets in Endocannabinoid Signaling.
TLDR
Current knowledge of the endocannabinoid system including metabolic enzymes involved in biosynthesis and degradation and their receptors are examined, and potential druggable targets for therapeutic intervention are evaluated.
Druggable Lipid Signaling Pathways
TLDR
This review series of “Druggable Lipid Signaling Pathways” provides 9 outstanding reviews that summarize the currently available drugs that target lipid signaling pathways and also outlines future directions for drug discovery.

References

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A complex homozygous mutation in ABHD12 responsible for PHARC syndrome discovered with NGS and review of the literature
TLDR
A new complex homozygous mutation c.379_385delAACTACTinsGATTCCTTATATACCATTGTAGTCTTACTGCTTTTGGTGAACACA (p.Asn127Aspfs*23) is detected in a 36‐year‐old man, which suggests that the involvement of ABHD12 in polyneuropathies is possibly underestimated.
Exome sequencing extends the phenotypic spectrum for ABHD12 mutations: from syndromic to nonsyndromic retinal degeneration.
Mutations in ABHD12 cause the neurodegenerative disease PHARC: An inborn error of endocannabinoid metabolism.
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It is shown that PHARC has phenotypic variability, even within a family, which is consistent with previous reports, and mutation analysis is a useful tool for confirming the diagnosis.
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