Structural variation and missense mutation in SBDS associated with Shwachman-Diamond Syndrome

dc.creatorFonseca, Claudia Marcia Benedetto de Carvalho
dc.creatorZuccherato, Luciana Werneck e
dc.creatorWilliams, Christopher L
dc.creatorNeill, Nicholas J
dc.creatorMurdock, David R
dc.creatorBainbridge, Matthew
dc.creatorJhangiani, Shalini N
dc.creatorMuzny, Donna M
dc.creatorGibbs, Richard A
dc.creatorIp, Wan
dc.creatorGuillerman, Robert Paul
dc.creatorLupski, James R
dc.creatorBertuch, Alison A
dc.date2015-02-19T14:39:14Z
dc.date2015-02-19T14:39:14Z
dc.date2014
dc.date.accessioned2023-09-26T23:07:50Z
dc.date.available2023-09-26T23:07:50Z
dc.identifierCARVALHO, 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
dc.identifier1471-2350
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/9499
dc.identifier10.1186/1471-2350-15-64
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8887189
dc.descriptionBACKGROUND: 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherBioMed Central
dc.rightsopen access
dc.subjectShwachman-Diamond syndrome
dc.subjectSBDS
dc.subjectStructural variation
dc.subjectGenomic rearrangement
dc.subjectNon-allelic homologous recombination
dc.subjectLow copy repeat
dc.subjectWhole exome sequencing
dc.subjectRecessive disease
dc.titleStructural variation and missense mutation in SBDS associated with Shwachman-Diamond Syndrome
dc.typeArticle


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