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

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

Research output: Contribution to journalArticle

11 Citations (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.

Original languageEnglish
Pages (from-to)438-442
Number of pages5
JournalMolecular Genetics and Metabolism
Volume105
Issue number3
DOIs
Publication statusPublished - Mar 2012

Fingerprint

Mucopolysaccharidosis IV
Uniparental Disomy
Chromosomes, Human, Pair 16
Chromosomes
Genes
Mothers
Microsatellite Repeats
N-acetylglucosamine-6-sulfatase
Mutation
Sulfatases
Developmental Bone Disease
Phenotype
Paternity
Genetic Counseling
Bone
Meiosis
Missense Mutation
Intelligence
Fathers
Catalytic Domain

Keywords

  • Chromosome 16
  • GALNS
  • Morquio A syndrome
  • MPS IVA
  • Uniparental disomy
  • UPD

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Morquio A syndrome due to Maternal Uniparental Isodisomy of the telomeric end of chromosome 16. / Catarzi, S.; Giunti, L.; Papadia, F.; Gabrielli, O.; Guerrini, R.; Donati, M. A.; Genuardi, M.; Morrone, A.

In: Molecular Genetics and Metabolism, Vol. 105, No. 3, 03.2012, p. 438-442.

Research output: Contribution to journalArticle

Catarzi, S, Giunti, L, Papadia, F, Gabrielli, O, Guerrini, R, Donati, MA, Genuardi, M & Morrone, A 2012, 'Morquio A syndrome due to Maternal Uniparental Isodisomy of the telomeric end of chromosome 16', Molecular Genetics and Metabolism, vol. 105, no. 3, pp. 438-442. https://doi.org/10.1016/j.ymgme.2011.11.196
Catarzi, S. ; Giunti, L. ; Papadia, F. ; Gabrielli, O. ; Guerrini, R. ; Donati, M. A. ; Genuardi, M. ; Morrone, A. / Morquio A syndrome due to Maternal Uniparental Isodisomy of the telomeric end of chromosome 16. In: Molecular Genetics and Metabolism. 2012 ; Vol. 105, No. 3. pp. 438-442.
@article{d96e6f61506c4255a9cfbc0f9b3c8c18,
title = "Morquio A syndrome due to Maternal Uniparental Isodisomy of the telomeric end of chromosome 16",
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.",
keywords = "Chromosome 16, GALNS, Morquio A syndrome, MPS IVA, Uniparental disomy, UPD",
author = "S. Catarzi and L. Giunti and F. Papadia and O. Gabrielli and R. Guerrini and Donati, {M. A.} and M. Genuardi and A. Morrone",
year = "2012",
month = "3",
doi = "10.1016/j.ymgme.2011.11.196",
language = "English",
volume = "105",
pages = "438--442",
journal = "Molecular Genetics and Metabolism",
issn = "1096-7192",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Morquio A syndrome due to Maternal Uniparental Isodisomy of the telomeric end of chromosome 16

AU - Catarzi, S.

AU - Giunti, L.

AU - Papadia, F.

AU - Gabrielli, O.

AU - Guerrini, R.

AU - Donati, M. A.

AU - Genuardi, M.

AU - Morrone, A.

PY - 2012/3

Y1 - 2012/3

N2 - 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.

AB - 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.

KW - Chromosome 16

KW - GALNS

KW - Morquio A syndrome

KW - MPS IVA

KW - Uniparental disomy

KW - UPD

UR - http://www.scopus.com/inward/record.url?scp=84858292060&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858292060&partnerID=8YFLogxK

U2 - 10.1016/j.ymgme.2011.11.196

DO - 10.1016/j.ymgme.2011.11.196

M3 - Article

C2 - 22178352

AN - SCOPUS:84858292060

VL - 105

SP - 438

EP - 442

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

IS - 3

ER -