PREPL deficiency: Delineation of the phenotype and development of a functional blood assay

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
  • Luc Régal
  • Emma Mårtensson
  • Isabelle Maystadt
  • Nicol Voermans
  • Damien Lederer
  • Alberto Burlina
  • María Jesús Juan Fita
  • A. Jeannette M. Hoogeboom
  • Mia Olsson Engman
  • Tess Hollemans
  • Meyke Schouten
  • Sandra Meulemans
  • Tord Jonson
  • Inge François
  • David Gil Ortega
  • Erik Jan Kamsteeg
  • John W.M. Creemers
Enheter & grupper
Externa organisationer
  • Catholic University of Leuven
  • Universitair Ziekenhuis Brussel
  • Skåne University Hospital
  • Institut de Pathologie et Génétique
  • Radboud University Nijmegen
  • University Hospital of Padua
  • Hospital Virgen de la Arrixaca
  • Erasmus University Medical Center
  • Blekinge Hospital
  • University Hospitals Leuven
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Pediatrik

Nyckelord

Originalspråkengelska
Sidor (från-till)109-118
Antal sidor10
TidskriftGenetics in Medicine
Volym20
Utgivningsnummer1
StatusPublished - 2018 jan 1
PublikationskategoriForskning
Peer review utfördJa