Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation

Raul E. Piña-Aguilar; Gerardo R. Zaragoza-Arévalo; Isabella Rau; Andreas Gal; Miguel A. Alcántara-Ortigoza; Mónica S. López-Martínez; Yuritzi Santillán-Hernández

doi:10.1016/j.ejmg.2012.11.006

Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation

Raul E. Piña-Aguilar, Gerardo R. Zaragoza-Arévalo, Isabella Rau, Andreas Gal, Miguel A. Alcántara-Ortigoza, Mónica S. López-Martínez, Yuritzi Santillán-Hernández^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

We report a Mexican girl showing the full blown clinical picture of mucopolysaccharidosis type II (MPSII). Iduronate-2-sulfatase (IDS) activity was low and she carried a heterozygous de novo c.1327C>T transition in exon 9, that changes codon 443 for a premature stop (TGA; p.Arg443^*). Analysis of X-chromosome inactivation in androgen receptor (AR) locus showed a highly skewed ratio of 92:8 suggesting a functional hemizygosity with dominant expression of the mutant IDS and explaining the disease manifestation. This is one of the rare cases of females affected by MPSII due to the combined effect of a skewed X-chromosome inactivation and a de novo IDS mutation. We recommend that clinicians should consider the diagnosis of MPSII even in a girl without positive family history for this condition.

Original language	English
Pages (from-to)	159-162
Number of pages	4
Journal	European Journal of Medical Genetics
Volume	56
Issue number	3
Early online date	8 Dec 2012
DOIs	https://doi.org/10.1016/j.ejmg.2012.11.006
Publication status	Published - Mar 2013
Event	12th International Symposium on MPS and Related Diseases - Noordwijkerhout, Netherlands Duration: 28 Jun 2012 → 1 Jul 2012

Bibliographical note

We are very grateful to the family of the patient that, in spite of the pain of having their daughter suffering of MPS and later the pain of losing her, cooperated with us and agreed to the publication of this case.

We thank the Laboratory of Genetics from CMN “20 de Noviembre” ISSSTE, especially to M. Concepcion Yerena de Vega, for cytogenetic analysis of the case. We are also grateful to Dr. Joaquín Carrillo-Farga from Instituto de Hematopatologia, Mexico for his expertise in blood smear analysis and to Dr. Paula A. Rozenfeld from LISIN, Argentina for enzymatic analysis.

Keywords

Elaprase®
Hunter syndrome
Iduronate-2-sulfatase
Mexico
MPSII
X-linked disease

Access to Document

10.1016/j.ejmg.2012.11.006Licence: Unspecified

Cite this

Piña-Aguilar, R. E., Zaragoza-Arévalo, G. R., Rau, I., Gal, A., Alcántara-Ortigoza, M. A., López-Martínez, M. S., & Santillán-Hernández, Y. (2013). Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation. European Journal of Medical Genetics, 56(3), 159-162. https://doi.org/10.1016/j.ejmg.2012.11.006

Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation. / Piña-Aguilar, Raul E.; Zaragoza-Arévalo, Gerardo R.; Rau, Isabella et al.
In: European Journal of Medical Genetics, Vol. 56, No. 3, 03.2013, p. 159-162.

Research output: Contribution to journal › Article › peer-review

Piña-Aguilar, RE, Zaragoza-Arévalo, GR, Rau, I, Gal, A, Alcántara-Ortigoza, MA, López-Martínez, MS & Santillán-Hernández, Y 2013, 'Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation', European Journal of Medical Genetics, vol. 56, no. 3, pp. 159-162. https://doi.org/10.1016/j.ejmg.2012.11.006

Piña-Aguilar RE, Zaragoza-Arévalo GR, Rau I, Gal A, Alcántara-Ortigoza MA, López-Martínez MS et al. Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation. European Journal of Medical Genetics. 2013 Mar;56(3):159-162. Epub 2012 Dec 8. doi: 10.1016/j.ejmg.2012.11.006

@article{6a66bb66b2334f7ea5a3cf344852dc98,

title = "Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation",

abstract = "We report a Mexican girl showing the full blown clinical picture of mucopolysaccharidosis type II (MPSII). Iduronate-2-sulfatase (IDS) activity was low and she carried a heterozygous de novo c.1327C>T transition in exon 9, that changes codon 443 for a premature stop (TGA; p.Arg443*). Analysis of X-chromosome inactivation in androgen receptor (AR) locus showed a highly skewed ratio of 92:8 suggesting a functional hemizygosity with dominant expression of the mutant IDS and explaining the disease manifestation. This is one of the rare cases of females affected by MPSII due to the combined effect of a skewed X-chromosome inactivation and a de novo IDS mutation. We recommend that clinicians should consider the diagnosis of MPSII even in a girl without positive family history for this condition.",

keywords = "Elaprase{\textregistered}, Hunter syndrome, Iduronate-2-sulfatase, Mexico, MPSII, X-linked disease",

author = "Pi{\~n}a-Aguilar, {Raul E.} and Zaragoza-Ar{\'e}valo, {Gerardo R.} and Isabella Rau and Andreas Gal and Alc{\'a}ntara-Ortigoza, {Miguel A.} and L{\'o}pez-Mart{\'i}nez, {M{\'o}nica S.} and Yuritzi Santill{\'a}n-Hern{\'a}ndez",

note = "We are very grateful to the family of the patient that, in spite of the pain of having their daughter suffering of MPS and later the pain of losing her, cooperated with us and agreed to the publication of this case. We thank the Laboratory of Genetics from CMN “20 de Noviembre” ISSSTE, especially to M. Concepcion Yerena de Vega, for cytogenetic analysis of the case. We are also grateful to Dr. Joaqu{\'i}n Carrillo-Farga from Instituto de Hematopatologia, Mexico for his expertise in blood smear analysis and to Dr. Paula A. Rozenfeld from LISIN, Argentina for enzymatic analysis.; 12th International Symposium on MPS and Related Diseases ; Conference date: 28-06-2012 Through 01-07-2012",

year = "2013",

month = mar,

doi = "10.1016/j.ejmg.2012.11.006",

language = "English",

volume = "56",

pages = "159--162",

journal = "European Journal of Medical Genetics",

issn = "1769-7212",

publisher = "Elsevier Masson SAS",

number = "3",

}

TY - JOUR

T1 - Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation

AU - Piña-Aguilar, Raul E.

AU - Zaragoza-Arévalo, Gerardo R.

AU - Rau, Isabella

AU - Gal, Andreas

AU - Alcántara-Ortigoza, Miguel A.

AU - López-Martínez, Mónica S.

AU - Santillán-Hernández, Yuritzi

N1 - We are very grateful to the family of the patient that, in spite of the pain of having their daughter suffering of MPS and later the pain of losing her, cooperated with us and agreed to the publication of this case. We thank the Laboratory of Genetics from CMN “20 de Noviembre” ISSSTE, especially to M. Concepcion Yerena de Vega, for cytogenetic analysis of the case. We are also grateful to Dr. Joaquín Carrillo-Farga from Instituto de Hematopatologia, Mexico for his expertise in blood smear analysis and to Dr. Paula A. Rozenfeld from LISIN, Argentina for enzymatic analysis.

PY - 2013/3

Y1 - 2013/3

N2 - We report a Mexican girl showing the full blown clinical picture of mucopolysaccharidosis type II (MPSII). Iduronate-2-sulfatase (IDS) activity was low and she carried a heterozygous de novo c.1327C>T transition in exon 9, that changes codon 443 for a premature stop (TGA; p.Arg443*). Analysis of X-chromosome inactivation in androgen receptor (AR) locus showed a highly skewed ratio of 92:8 suggesting a functional hemizygosity with dominant expression of the mutant IDS and explaining the disease manifestation. This is one of the rare cases of females affected by MPSII due to the combined effect of a skewed X-chromosome inactivation and a de novo IDS mutation. We recommend that clinicians should consider the diagnosis of MPSII even in a girl without positive family history for this condition.

AB - We report a Mexican girl showing the full blown clinical picture of mucopolysaccharidosis type II (MPSII). Iduronate-2-sulfatase (IDS) activity was low and she carried a heterozygous de novo c.1327C>T transition in exon 9, that changes codon 443 for a premature stop (TGA; p.Arg443*). Analysis of X-chromosome inactivation in androgen receptor (AR) locus showed a highly skewed ratio of 92:8 suggesting a functional hemizygosity with dominant expression of the mutant IDS and explaining the disease manifestation. This is one of the rare cases of females affected by MPSII due to the combined effect of a skewed X-chromosome inactivation and a de novo IDS mutation. We recommend that clinicians should consider the diagnosis of MPSII even in a girl without positive family history for this condition.

KW - Elaprase®

KW - Hunter syndrome

KW - Iduronate-2-sulfatase

KW - Mexico

KW - MPSII

KW - X-linked disease

UR - http://www.scopus.com/inward/record.url?scp=84874314465&partnerID=8YFLogxK

U2 - 10.1016/j.ejmg.2012.11.006

DO - 10.1016/j.ejmg.2012.11.006

M3 - Article

C2 - 23232253

AN - SCOPUS:84874314465

SN - 1769-7212

VL - 56

SP - 159

EP - 162

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

IS - 3

T2 - 12th International Symposium on MPS and Related Diseases

Y2 - 28 June 2012 through 1 July 2012

ER -

Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this