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

  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},
Genotype‐phenotype correlation in a novel ABHD12 mutation underlying PHARC syndrome
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
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
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.
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Atypical and ultra-rare Usher syndrome: a review
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Dark-adapted threshold and electroretinogram for diagnosis of Usher syndrome
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.
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.
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
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A complex homozygous mutation in ABHD12 responsible for PHARC syndrome discovered with NGS and review of the literature
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.
Novel ABHD12 Mutations in PHARC Patients
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.
Charcot-Marie-Tooth disease
The relatively high frequency of GDAP1 mutations, coupled with the scarceness of MFN2 mutations, and the high proportion of recessive inheritance in this series exemplify the particularity of the genetic distribution of Charcot-Marie-Tooth disease in this region.
Differential diagnosis of Charcot-Marie-Tooth disease and related neuropathies
A number of clinical, laboratory, electrophysiological, morphological and neuroradiological features that may help in the diagnostic process are reviewed in the present paper and DNA investigations are fundamental but need to be properly addressed.
ABHD12 controls brain lysophosphatidylserine pathways that are deregulated in a murine model of the neurodegenerative disease PHARC
Untargeted metabolomics combined with a genetic mouse model is used to determine that the poorly characterized serine hydrolase α/β-hydrolase domain-containing (ABHD)12, mutations in which cause the human neurodegenerative disorder PHARC, is a principal LPS lipase in the mammalian brain.
Biochemical and pharmacological characterization of human α/β-hydrolase domain containing 6 (ABHD6) and 12 (ABHD12)[S]
Inhibitor profiling revealed striking potency differences between hAB HD6 and hABHD12, a finding that, when combined with the substrate profiling data, should facilitate further efforts toward the design of potent and selective inhibitors, especially those targeting hABhd12, which currently lacks such inhibitors.