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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Ogata, Tsutomu / Toppari, Jorma

12 Issues per year


IMPACT FACTOR 2017: 1.086

CiteScore 2017: 1.07

SCImago Journal Rank (SJR) 2017: 0.465
Source Normalized Impact per Paper (SNIP) 2017: 0.580

Online
ISSN
2191-0251
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Volume 25, Issue 9-10

Issues

A novel intronic mutation in SHOX causes short stature by disrupting a splice acceptor site: direct demonstration of aberrant splicing by expression of a minigene in HEK-293T cells

Jennifer Danzig
  • Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
  • Other articles by this author:
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/ Michael A. Levine
  • Corresponding author
  • Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2012-08-11 | DOI: https://doi.org/10.1515/jpem-2012-0173

Abstract

SHOX, the short stature homeobox-containing gene, encodes a critical regulatory protein controlling long bone growth. We examined patients in one family, identified an intronic mutation, and expressed SHOX minigenes in HEK293T cells to characterize the effect on gene splicing. We identified a novel mutation at position –3 (c.-432-3C>A;g.6120C>A) of the intron 1 splice acceptor site; three short (height Z-score –2.4 to –1.7) children were heterozygous and the father (height Z-score –3.4) was homozygous. A wild-type minigene produced alternative transcripts; one utilized the normal splice site between intron 1 and exon 2, the other a cryptic splice site in exon 2. Mutant SHOX minigene generated only the smaller transcript. The exon 2 acceptor splice site is weak; an alternative transcript is normally produced using a downstream cryptic splice site. The c.-432-3C>A mutation causes further weakening, and the cryptic splice site is preferentially utilized, resulting in SHOX deficiency and short stature.

Keywords: short stature; SHOX; splice site mutation

About the article

Corresponding author: Michael A. Levine, MD, Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, 11 Northwest Tower, Suite 30, 34th and Civic Center Boulevard, Philadelphia, PA 19104, USA, Phone: +1-215-590-3618, Fax: +1-215-590-3053


Received: 2012-06-04

Accepted: 2012-07-11

Published Online: 2012-08-11

Published in Print: 2012-10-01


Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 25, Issue 9-10, Pages 889–895, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2012-0173.

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©2012 by Walter de Gruyter Berlin Boston.Get Permission

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