Morquio A syndrome due to Maternal Uniparental Isodisomy of the telomeric end of chromosome 16

Maurizio Genuardi, S. Catarzi, L. Giunti, F. Papadia, O. Gabrielli, R. Guerrini, M. A. Donati, A. Morrone

Risultato della ricerca: Contributo in rivistaArticolo in rivista

13 Citazioni (Scopus)

Abstract

Morquio A syndrome (MPS IVA) is a recessive lysosomal storage disorder (LSD) caused by mutations in the GALNS gene leading to the deficiency of lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Patients show a broad spectrum of phenotypes ranging from classical severe type to mild forms. Classical forms are characterized by severe bone dysplasia and usually normal intelligence. So far, more than 170 unique mutations have been identified in the GALNS gene of MPS IVA patients. We report on a Morquio A patient with a classical phenotype who was found to be homozygous for a missense mutation (c.236 G > A: p.Cys79Tyr) in the GALNS gene. This alteration affects the highly conserved p.Cys79 that is transformed into formylglycine, the catalytic residue of the active site. The mutation was present in the proband's mother, but not in the father, whose paternity was confirmed by microsatellite analysis. In order to test the hypothesis of maternal uniparental disomy (UPD), we investigated the segregation of sixteen microsatellite markers from chromosome 16. The results showed a condition of maternal UPD due to an error in meiosis I. Maternal isodisomy of the 16q24 region led to homozygosity for the GALNS mutant allele, causing the patient's disease. These findings allow to add for the first time the LSD Morquio A syndrome to the list of conditions that can be caused by UPD. The possibility of UPD is relevant when giving genetic counseling to couples since the recurrent risk in future pregnancies is dramatically reduced. (C) 2011 Elsevier Inc. All rights reserved.
Lingua originaleEnglish
pagine (da-a)438-442
Numero di pagine5
RivistaMolecular Genetics and Metabolism
Volume105
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • DEFICIENCY
  • DISEASE
  • DISOMY UPD
  • ENZYME
  • FORMYLGLYCINE
  • GALNS GENE
  • HUMAN N-ACETYLGALACTOSAMINE-6-SULFATE SULFATASE
  • MPS-IV-A
  • MUCOPOLYSACCHARIDOSIS IVA
  • PHENOTYPES

Fingerprint

Entra nei temi di ricerca di 'Morquio A syndrome due to Maternal Uniparental Isodisomy of the telomeric end of chromosome 16'. Insieme formano una fingerprint unica.

Cita questo