Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/9499
Title: Structural variation and missense mutation in SBDS associated with Shwachman-Diamond Syndrome
Authors: Fonseca, Claudia Marcia Benedetto de Carvalho
Zuccherato, Luciana Werneck e
Williams, Christopher L
Neill, Nicholas J
Murdock, David R
Bainbridge, Matthew
Jhangiani, Shalini N
Muzny, Donna M
Gibbs, Richard A
Ip, Wan
Guillerman, Robert Paul
Lupski, James R
Bertuch, Alison A
Affilliation: Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA.
Baylor College of Medicine. Department of Pediatrics. Houston, TX, USA.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA.
Baylor College of Medicine. Human Genome Sequencing Center. Houston, TX, USA
Baylor College of Medicine. Human Genome Sequencing Center. Houston, TX, USA
Baylor College of Medicine. Human Genome Sequencing Center. Houston, TX, USA
Baylor College of Medicine. Human Genome Sequencing Center. Houston, TX, USA
Baylor College of Medicine. Human Genome Sequencing Center. Houston, TX, USA
Hospital for Sick Children. Research Institute. Program in Physiology and Experimental Medicine. Toronto, Ontario, Canada.
Texas Children’s Hospital. Houston, TX, USA/ Baylor College of Medicine. Department of Radiology. Houston, TX, USA.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/ Baylor College of Medicine. Department of Pediatrics. Houston, TX, USA/Texas Children’s Hospital. Houston, TX, USA
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/ Baylor College of Medicine. Department of Pediatrics. Houston, TX, USA/Texas Children’s Hospital. Houston, TX, USA
Abstract: BACKGROUND: Shwachman-Diamond syndrome (SDS) is an autosomal recessive ribosomopathy caused mainly by compound heterozygous mutations in SBDS. Structural variation (SV) involving the SBDS locus has been rarely reported in association with the disease. We aimed to determine whether an SV contributed to the pathogenesis of a case lacking biallelic SBDS point mutations. CASE PRESENTATION: Whole exome sequencing was performed in a patient with SDS lacking biallelic SBDS point mutations. Array comparative genomic hybridization and Southern blotting were used to seek SVs across the SBDS locus. Locus-specific polymerase chain reaction (PCR) encompassing flanking intronic sequence was also performed to investigate mutation within the locus. RNA expression and Western blotting were performed to analyze allele and protein expression. We found the child harbored a single missense mutation in SBDS (c.98A > C; p.K33T), inherited from the mother, and an SV in the SBDS locus, inherited from the father. The missense allele and SV segregated in accordance with Mendelian expectations for autosomal recessive SDS. Complementary DNA and western blotting analysis and locus specific PCR support the contention that the SV perturbed SBDS protein expression in the father and child. CONCLUSION: Our findings implicate genomic rearrangements in the pathogenesis of some cases of SDS and support patients lacking biallelic SBDS point mutations be tested for SV within the SBDS locus.
Keywords: Shwachman-Diamond syndrome
SBDS
Structural variation
Genomic rearrangement
Non-allelic homologous recombination
Low copy repeat
Whole exome sequencing
Recessive disease
Issue Date: 2014
Publisher: BioMed Central
Citation: CARVALHO, Claudia Marcia Benedetto de et al. Structural variation and missense mutation in SBDS associated with Shwachman-Diamond Syndrome. BMC Medical Genetics 2014, v. 15, p. 64
DOI: 10.1186/1471-2350-15-64
ISSN: 1471-2350
Copyright: open access
Appears in Collections:MG - IRR - Artigos de Periódicos

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