title: A patient with PMP22-related hereditary neuropathy and DBH-gene-related dysautonomia.
abstract: Recurrent focal neuropathy with liability to pressure palsies is a relatively frequent autosomal-dominant demyelinating neuropathy linked to peripheral myelin protein 22 (PMP22) gene deletions. The combination of PMP22 gene mutations with other genetic variants is known to cause a more severe phenotype than expected. We present the case of a patient with severe orthostatic hypotension since 12 years of age, who inherited a PMP22 gene deletion from his father. Genetic double trouble was suspected because of selective sympathetic autonomic disturbances. Through exome-sequencing analysis, we identified two novel mutations in the dopamine beta hydroxylase gene. Moreover, with interactome analysis, we excluded a further influence on the origin of the disease by variants in other genes. This case increases the number of unique patients presenting with dopamine-β-hydroxylase deficiency and of cases with genetically proven double trouble. Finding the right, complete diagnosis is crucial to obtain adequate medical care and appropriate genetic counseling.
authors.affiliation: Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bartoletti-Stella
authors.affiliation: Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Chiaro
authors.affiliation: Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.|UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura 1/8, 40139, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Calandra-Buonaura
authors.affiliation: Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.|UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura 1/8, 40139, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Contin
authors.affiliation: UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura 1/8, 40139, Bologna, Italy.
authors.forename: Cesa
authors.initials: C
authors.lastname: Scaglione
authors.affiliation: Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.|UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura 1/8, 40139, Bologna, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Barletta
authors.affiliation: UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura 1/8, 40139, Bologna, Italy.
authors.forename: Annagrazia
authors.initials: A
authors.lastname: Cecere
authors.affiliation: Interdepartmental Centre "L. Galvani" (CIG), Alma Mater Studiorum University of Bologna, Piazza di Porta San Donato 1, 40126, Bologna, Italy.|Department of Experimental, Diagnostic and Specialty Medicine Experimental Pathology, Alma Mater Studiorum University of Bologna, Via S. Giacomo 12, 40126, Bologna, Italy.|Center for Applied Biomedical Research, St. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138, Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Garagnani
authors.affiliation: CNR Consiglio Nazionale delle Ricerche, IAC Istituto per le Applicazioni del Calcolo "Mauro Picone", Via dei Taurini 19, 00185, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tieri
authors.affiliation: Department of Biotechnologies, University of Verona, Strada Le Grazie 15, 37134, Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferrarini
authors.affiliation: UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura 1/8, 40139, Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Piras
authors.affiliation: UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura 1/8, 40139, Bologna, Italy.|Department of Experimental, Diagnostic and Specialty Medicine Experimental Pathology, Alma Mater Studiorum University of Bologna, Via S. Giacomo 12, 40126, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Department of Biotechnologies, University of Verona, Strada Le Grazie 15, 37134, Verona, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Delledonne
authors.affiliation: Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy. pietro.cortelli@unibo.it.|UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura 1/8, 40139, Bologna, Italy. pietro.cortelli@unibo.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
authors.affiliation: Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy. sabina.capellari@unibo.it.|UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura 1/8, 40139, Bologna, Italy. sabina.capellari@unibo.it.
authors.forename: Sabina
authors.initials: S
authors.lastname: Capellari
mesh_terms: D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000151:congenital*; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency*; D004402:Dysautonomia, Familial / Q000235:genetics; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics*; D006801:Humans; D009185:Myelin Proteins / Q000235:genetics*; D009638:Norepinephrine / Q000172:deficiency*
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine
keywords: Dopamine-β-hydroxylase deficiency; Exome sequencing, dysautonomia; Recurrent focal neuropathy with liability to pressure palsies