{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:33:05Z","timestamp":1747186385138,"version":"3.40.5"},"reference-count":7,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Biallelic mutations in the <jats:italic>PTRH2<\/jats:italic> gene have been associated with infantile multisystem neurological, endocrine, and pancreatic disease (IMNEPD), a rare autosomal recessive disorder of variable expressivity characterized by global developmental delay, intellectual disability or borderline IQ level, sensorineural hearing loss, ataxia, and pancreatic insufficiency. Various additional features may be included, such as peripheral neuropathy, facial dysmorphism, hypothyroidism, hepatic fibrosis, postnatal microcephaly, cerebellar atrophy, and epilepsy. Here, we report the first Italian family presenting only predominant neurological features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Extensive neurological and neurophysiological evaluations have been conducted on the two affected brothers and their healthy mother since 1996. The diagnosis of peripheral neuropathy of probable hereditary origin was confirmed through a sural nerve biopsy. Exome sequencing was performed after the analysis of major neuropathy\u2010associated genes yielded negative results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Whole\u2010exome sequencing analysis identified the homozygous substitution c.256C&gt;T (p.Gln86Ter) in the <jats:italic>PTRH2<\/jats:italic> gene in the two siblings. According to American College of Medical Genetics and Genomics (ACMG) guidelines, the variant has been classified as pathogenic.<\/jats:p><jats:p>At 48\u2009years old, the proband's reevaluation confirmed a demyelinating sensorimotor polyneuropathy with bilateral sensorineural hearing loss that had been noted since he was 13. Additionally, drug\u2010resistant epileptic seizures occurred when he was 32\u2009years old. No hepatic or endocrinological signs developed. The younger affected brother, 47\u2009years old, has an overlapping clinical presentation without epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our findings expand the clinical phenotype and further demonstrate the clinical heterogeneity related to <jats:italic>PTRH2<\/jats:italic> variants. We thereby hope to better define IMNEPD and facilitate the identification and diagnosis of this novel disease entity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jns.12636","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T11:15:38Z","timestamp":1718363738000},"page":"279-285","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The neurological core features of the infantile\u2010onset multisystem neurologic, endocrine, and pancreatic disease: A novel nonsense mutation in an Italian family"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7683-9449","authenticated-orcid":false,"given":"Alessia","family":"Mammi","sequence":"first","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, UOC Medical Genetics  Genoa Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences University of Genoa  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2208-9195","authenticated-orcid":false,"given":"Alessandro","family":"Geroldi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences University of Genoa  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Patrone","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences University of Genoa  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Gotta","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, UOC Medical Genetics  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Origone","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, UOC Medical Genetics  Genoa Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences University of Genoa  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Gaudio","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, UOC Medical Genetics  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"La Barbera","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, UOC Medical Genetics  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Sanguineri","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, UOC Medical Genetics  Genoa Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences University of Genoa  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarissa","family":"Ponti","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, UOC Medical Genetics  Genoa Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences University of Genoa  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Iacomino","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Giannina Gaslini, Medical Genetic Unit  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Traverso","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Giannina Gaslini, Medical Genetic Unit  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edoardo","family":"Ferlazzo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences Magna Graecia University of Catanzaro  Catanzaro Italy"},{"name":"Regional Epilepsy Centre, \u201cBianchi\u2010Melacrino\u2010Morelli\u201d Great Metropolitan Hospital  Reggio Calabria Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Schenone","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences University of Genoa  Genoa Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, UOC Neurology Clinic  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Pascarella","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences Magna Graecia University of Catanzaro  Catanzaro 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