PREPL deficiency: delineation of the phenotype and development of a functional blood assay
| Autor: | Luc Régal, Erik-Jan Kamsteeg, Damien Lederer, Nicol C. Voermans, Alberto Burlina, John W.M. Creemers, David Gil Ortega, Sandra Meulemans, Tord Jonson, Mia Olsson Engman, A. Jeannette M. Hoogeboom, Meyke Schouten, Emma Mårtensson, María Jesús Juan Fita, Tess Hollemans, Isabelle Maystadt, Inge Francois |
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| Přispěvatelé: | Clinical Genetics, Erasmus MC other, Pediatrics, Faculty of Psychology and Educational Sciences |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Pathology blood assay Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] Ptosis Genetics(clinical) Child Genetics (clinical) Comparative Genomic Hybridization medicine.diagnostic_test Serine Endopeptidases Facial weakness Cystinuria Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] PREPL Phenotype Child Preschool Female medicine.symptom Prolyl Oligopeptidases Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] Adult congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Adolescent Growth hormone deficiency neonatal hypotonia8Prader-Willi syndrome 03 medical and health sciences Young Adult All institutes and research themes of the Radboud University Medical Center medicine Blood test Humans Genetic Predisposition to Disease Allele Genetic Association Studies Chromosome Aberrations business.industry Infant Newborn Facies Infant medicine.disease nervous system diseases Enzyme Activation hypotonia-cystinuria syndrome 030104 developmental biology Neonatal hypotonia business |
| Zdroj: | Genetics in Medicine, 20, 109-118 Genetics in Medicine, 20(1), 109-118. Lippincott Williams & Wilkins Genetics in Medicine, 20, 1, pp. 109-118 |
| ISSN: | 1530-0366 1098-3600 |
| Popis: | PurposePREPL deficiency causes neonatal hypotonia, ptosis, neonatal feeding difficulties, childhood obesity, xerostomia, and growth hormone deficiency. Different recessive contiguous gene deletion syndromes involving PREPL and a variable combination of SLC3A1 (hypotonia-cystinuria syndrome), CAMKMT (atypical hypotonia-cystinuria syndrome), and PPM1B (2p21 deletion syndrome) have been described. In isolated PREPL deficiency, previously described only once, the absence of cystinuria complicates the diagnosis. Therefore, we developed a PREPL blood assay and further delineated the phenotype.MethodsClinical features of new subjects with PREPL deficiency were recorded. The presence of PREPL in lymphocytes and its reactivity with an activity-based probe were evaluated by western blot.ResultsFive subjects with isolated PREPL deficiency, three with hypotonia-cystinuria syndrome, and two with atypical hypotonia-cystinuria syndrome had nine novel alleles. Their IQs ranged from 64 to 112. Adult neuromuscular signs included ptosis, nasal dysarthria, facial weakness, and variable proximal and neck flexor weakness. Autonomic features are prevalent. PREPL protein and reactivity were absent in lymphocytes from subjects with PREPL deficiency, but normal in the clinically similar Prader-Willi syndrome.ConclusionPREPL deficiency causes neuromuscular, autonomic, cognitive, endocrine, and dysmorphic clinical features. PREPL is not deficient in Prader-Willi syndrome. The novel blood test should facilitate the confirmation of PREPL deficiency. |
| Databáze: | OpenAIRE |
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