A patient with PMP22-related hereditary neuropathy and DBH-gene-related dysautonomia

Anna Bartoletti-Stella, Giacomo Chiaro, Giovanna Calandra-Buonaura, Manuela Contin, Cesa Scaglione, Giorgio Barletta, Annagrazia Cecere, Paolo Garagnani, Paolo Tieri, Alberto Ferrarini, Silvia Piras, Claudio Franceschi, Massimo Delledonne, Pietro Cortelli, Sabina Capellari

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.