Expanding the Mutational Spectrum in Johanson-Blizzard Syndrome: Identification of Whole Exon Deletions and Duplications in the Ubr1 Gene by Multiplex Ligation-Dependent Probe Amplification Analysis

Expanding the Mutational Spectrum in Johanson-Blizzard Syndrome: Identification of Whole Exon Deletions and Duplications in the Ubr1 Gene by Multiplex Ligation-Dependent Probe Amplification Analysis Publisher Pubmed

Sukalo M¹ ; Schaflein E^{2, 3} ; Schanze I¹ ; Everman DB⁴ ; Rezaei N^{5, 6} ; Argente J^{7, 8, 9} ; Lordasanchez I¹⁰ ; Deshpande C¹¹ ; Takahashi T¹² ; Kleger A¹³ ; Zenker M¹

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1. Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany
2. Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany
3. Department of Psychosomatic Medicine and Psychotherapy, University Hospital Rechts der Isar, Technische Universitat Munchen, Munich, Germany
4. Greenwood Genetic Center, Greenwood, SC, United States
5. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
6. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sheffield, United Kingdom
7. Departments of Endocrinology and Pediatrics and Instituto de Investigacion La Princesa, Hospital Infantil Universitario Nino Jesus, Madrid, Spain
8. Department of Pediatrics, Universidad Autonoma de Madrid, Madrid, Spain
9. Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
10. Department of Genetics, IIS-Fundacion Jimenez Diaz UAM, CIBERER, Madrid, Spain
11. Clinical Genetics, Guy's Hospital, London, United Kingdom
12. Department of Pediatrics, Akita University Graduate School of Medicine, Akita, Japan
13. Department of Internal Medicine I, University Medical Center Ulm, Ulm, Germany

Source: Molecular Genetics and Genomic Medicine Published:2017

Abstract

Background: Johanson-Blizzard syndrome (JBS, MIM #243800) is a very rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, nasal wing hypoplasia, hypodontia, and other abnormalities. JBS is caused by mutations of the UBR1 gene (MIM *605981), encoding a ubiquitin ligase of the N-end rule pathway. Methods: Molecular findings in a total of 65 unrelated patients with a clinical diagnosis of JBS who were previously screened for UBR1 mutations by Sanger sequencing were reviewed and cases lacking a disease-causing UBR1 mutation on either one or both alleles were included in this study. In order to discover mutations that are not detectable by Sanger sequencing, we designed a probe set for multiplex ligation-dependent probe amplification (MLPA) analysis of the UBR1 gene and analyzed the copy number status of all 47 UBR1 exons. Results: Our previous studies using Sanger sequencing could detect mutations in 93.1% of 130 disease-associated UBR1 alleles. Six patients with a highly suggestive clinical diagnosis of JBS and unsolved genotype were included in this study. MLPA analysis detected six alleles harboring exon deletions/duplications, thereby raising the mutation detection rate in the entire cohort to 97.7% (127/130 alleles). Conclusion: We conclude that single or multi-exon deletions or duplications account for a substantial proportion of JBS-associated UBR1 mutations. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

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MLA	Sukalo M, et al.. "Expanding the Mutational Spectrum in Johanson-Blizzard Syndrome: Identification of Whole Exon Deletions and Duplications in the Ubr1 Gene by Multiplex Ligation-Dependent Probe Amplification Analysis." Molecular Genetics and Genomic Medicine, vol. 5, no. 6, 2017, pp. 774-780.
APA	Sukalo M, Schaflein E, Schanze I, Everman DB, Rezaei N, Argente J, Lordasanchez I, Deshpande C, Takahashi T, Kleger A, Zenker M (2017). Expanding the Mutational Spectrum in Johanson-Blizzard Syndrome: Identification of Whole Exon Deletions and Duplications in the Ubr1 Gene by Multiplex Ligation-Dependent Probe Amplification Analysis. Molecular Genetics and Genomic Medicine, 5(6), 774-780.
Chicago	Sukalo M, Schaflein E, Schanze I, Everman DB, Rezaei N, Argente J, Lordasanchez I, et al.. "Expanding the Mutational Spectrum in Johanson-Blizzard Syndrome: Identification of Whole Exon Deletions and Duplications in the Ubr1 Gene by Multiplex Ligation-Dependent Probe Amplification Analysis." Molecular Genetics and Genomic Medicine 5, no. 6 (2017): 774-780.
Harvard	Sukalo M et al. (2017) 'Expanding the Mutational Spectrum in Johanson-Blizzard Syndrome: Identification of Whole Exon Deletions and Duplications in the Ubr1 Gene by Multiplex Ligation-Dependent Probe Amplification Analysis', Molecular Genetics and Genomic Medicine, 5(6), pp. 774-780.
Vancouver	Sukalo M, Schaflein E, Schanze I, Everman DB, Rezaei N, Argente J, et al.. Expanding the Mutational Spectrum in Johanson-Blizzard Syndrome: Identification of Whole Exon Deletions and Duplications in the Ubr1 Gene by Multiplex Ligation-Dependent Probe Amplification Analysis. Molecular Genetics and Genomic Medicine. 2017;5(6):774-780.
BibTex	@article{ author = {Sukalo M and Schaflein E and Schanze I and Everman DB and Rezaei N and Argente J and Lordasanchez I and Deshpande C and Takahashi T and Kleger A and Zenker M}, title = {Expanding the Mutational Spectrum in Johanson-Blizzard Syndrome: Identification of Whole Exon Deletions and Duplications in the Ubr1 Gene by Multiplex Ligation-Dependent Probe Amplification Analysis}, journal = {Molecular Genetics and Genomic Medicine}, volume = {5}, number = {6}, pages = {774-780}, year = {2017} }
RIS	TY - JOUR AU - Sukalo M AU - Schaflein E AU - Schanze I AU - Everman DB AU - Rezaei N AU - Argente J AU - Lordasanchez I AU - Deshpande C AU - Takahashi T AU - Kleger A AU - Zenker M TI - Expanding the Mutational Spectrum in Johanson-Blizzard Syndrome: Identification of Whole Exon Deletions and Duplications in the Ubr1 Gene by Multiplex Ligation-Dependent Probe Amplification Analysis JO - Molecular Genetics and Genomic Medicine VL - 5 IS - 6 SP - 774 EP - 780 PY - 2017 ER -

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