title: Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD.
abstract: Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity.
authors.affiliation: Department of Pediatric Neurology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.|Sozialpädiatrisches Zentrum (SPZ), Center for Chronically Sick Children, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.|Institute of Cell Biology and Neurobiology Charité - Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10115, Berlin, Germany.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Picker-Minh
authors.affiliation: Department of Genetics, AP-HP, Armand Trousseau Hospital, Avenue du Dr. Arnold-Netter 26, 75571, Paris, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Mignot
authors.affiliation: Department of Pediatric Neurology, AP-HP, Armand Trousseau Hospital, Avenue du Dr. Arnold-Netter 26, 75571, Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Doummar
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia.
authors.forename: Mais
authors.initials: M
authors.lastname: Hashem
authors.affiliation: Department of Pediatric Subspecialties, Children's Specialist Hospital, King Fahad Medical City, Riyadh, 59046, Saudi Arabia.
authors.forename: Eissa
authors.initials: E
authors.lastname: Faqeih
authors.affiliation: Department of Anatomy and Pathology, AP-HP, Armand Trousseau Hospital, Avenue du Dr. Arnold-Netter 26, 75571, Paris, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Josset
authors.affiliation: Department of Pediatric Nutrition and Gastroenterology, AP-HP, Armand Trousseau Hospital, Avenue du Dr. Arnold-Netter 26, 75571, Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Dubern
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia.
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
authors.affiliation: Department of Pediatric Neurology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.|Sozialpädiatrisches Zentrum (SPZ), Center for Chronically Sick Children, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.|Institute of Cell Biology and Neurobiology Charité - Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10115, Berlin, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kraemer
authors.affiliation: Department of Pediatric Neurology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany. angela.kaindl@charite.de.|Sozialpädiatrisches Zentrum (SPZ), Center for Chronically Sick Children, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany. angela.kaindl@charite.de.|Institute of Cell Biology and Neurobiology Charité - Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10115, Berlin, Germany. angela.kaindl@charite.de.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kaindl
mesh_terms: D002265:Carboxylic Ester Hydrolases / Q000235:genetics* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D010182:Pancreatic Diseases / Q000235:genetics* / Q000473:pathology*; D010375:Pedigree
chemical_list: D024101:Mitochondrial Proteins; D002265:Carboxylic Ester Hydrolases; C483418:PTH2 protein, human
keywords: Hepatosteatosis; Intellectual deficit; Motor delay; PTRH2; Pancreatic insufficiency; Peptidyl-tRNA hydrolase 2; Sensorineural deafness; Speech delay