Contents lists available at ScienceDirect Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns Clinical Short Communication Phenotypical features of two patients diagnosed with PHARC syndrome and carriers of a new homozygous mutation in the ABHD12 gene Marina Frasquet a , Vincenzo Lupo b , María José Chumillas c,d , Juan Francisco Vázquez-Costa a,d , Carmen Espinós b , Teresa Sevilla d,e,f, ⁎ a Neuromuscular Research Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain b Unit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders and Service of Genomics and Translational Genetics, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain c Department of Clinical Neurophysiology, Hospital Universitari i Politècnic La Fe, Valencia, Spain d Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain e Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain f Department of Medicine, University of Valencia, Valencia, Spain ARTICLE INFO Keywords: Charcot-Marie-Tooth disease ABHD12 gene PHARC Deaf-blindness Usher syndrome ABSTRACT PHARC (Polyneuropathy, Hearing loss, Ataxia, Retinitis pigmentosa and Cataracts) (MIM# 612674) is an au- tosomal recessive neurodegenerative disease caused by mutations in the ABHD12 gene. We evaluated two Spanish siblings affected with pes cavus, sensorimotor neuropathy, hearing loss, retinitis pigmentosa and ju- venile cataracts in whom the genetic test of ABHD12 revealed a novel homozygous frameshift mutation, c.211_223del (p.Arg71Tyrfs*26). The earliest clinical manifestation in these patients was a demyelinating neuropathy manifested with a Charcot-Marie-Tooth phenotype over three decades. Progressive hearing loss, cataracts and retinitis pigmentosa appeared after the age of 30. We herein describe the complete clinical picture of these two patients, and focus particularly on neuropathy characteristics. This study supports the fact that although PHARC is rare, its phenotype is very characteristic and we should include its study in patients affected with demyelinating polyneuropathy, hearing loss and retinopathy. 1. Introduction PHARC syndrome (MIM# 612674) is an autosomal recessive entity characterized by polyneuropathy, hearing loss, ataxia, retinitis pig- mentosa and cataracts. Some patients diagnosed with PHARC also show pyramidal tract signs or cerebellar signs, such as dysarthria, dysmetria or nystagmus. PHARC was first described by Fiskerstrand et al. [1] and it is caused by mutations in the ABHD12 gene, which encodes the en- zyme α/β hydrolase domain containing 12 [2]. By means of new gen- eration sequencing technologies, some PHARC cases have been found among families previously diagnosed with syndromic and non-syn- dromic retinitis pigmentosa [3] and deaf-blindness (Usher syndrome) [4,5]. We describe the phenotype of two Spanish patients with PHARC syndrome who harbour a novel homozygous frameshift mutation, c.211_223del (p.Arg71Tyrfs*26), in the ABHD12 gene. The description of this new family extends the spectrum of mutations in the ABHD12 gene associated with PHARC and aims to better define the neuropathy that forms part of this entity. 2. Material and methods Patients were assessed in the Neuromuscular Unit of a tertiary re- ferral centre in Valencia, Spain. The studied individuals comprised two affected siblings (II-1,II-3), their healthy parents and a healthy brother (II-5) (Fig. 1). All of them were clinically evaluated and underwent electrophysiological studies with standard techniques. The affected in- dividuals were thoroughly investigated and they had two different electrophysiological studies separated by an interval of 30 years. In the proband (II-3) the diagnosis was established by medical history and detailed evaluation of polyneuropathy and audiologic and ophtalmo- logical assessment. Peripheral neuropathy was classified as demyeli- nating Charcot-Marie-Tooth (CMT) phenotype according to motor nerve conduction velocities (MNCVs). Ophthalmological examination consisted of fundoscopy, standard electroretinogram (ERG), perimetry, and determination of visual acuity. Audiological study included: oto- scopic examination, otoacoustic emissions (OAEs), cochlear micro- phonics (CM), pure tone audiometry (PTA) and auditory brainstem response (ABR). DNA was obtained from the two affected siblings, their https://doi.org/10.1016/j.jns.2018.02.021 Received 7 November 2017; Received in revised form 19 January 2018; Accepted 6 February 2018 ⁎ Corresponding author at: Hospital Universitari i Politècnic la Fe, Department of Neurology, C/Fernando Abril Martorell, 106, 46026, Valencia, Spain. E-mail address: sevilla_ter@gva.es (T. Sevilla). Journal of the Neurological Sciences 387 (2018) 134–138 Available online 07 February 2018 0022-510X/ © 2018 Elsevier B.V. All rights reserved. T