Uncovering rare hematological entities: Shwachman Diamond syndrome in a pair of siblings with congenital neutropenia and recurrent infections

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F20%3A00073946" target="_blank" >RIV/65269705:_____/20:00073946 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41431-020-00739-z" target="_blank" >https://www.nature.com/articles/s41431-020-00739-z</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Uncovering rare hematological entities: Shwachman Diamond syndrome in a pair of siblings with congenital neutropenia and recurrent infections

Original language description

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder with clinical features that include pancreatic exocrine insufficiency, hematologic dysfunction, and skeletal abnormalities, Haematological malignancies occur in one third of patients. SDS is caused by homozygous or compound heterozygous mutations in SBDS gene. We present a sibling pair with mild to moderate neutropenia, episodes of autoimmune hemolysis and recurrent infections of the oral cavity and respiratory airways. Prior investigations were inconclusive. Family history suggested AR mode of inheritance. We performed whole-exome sequencing of siblings and parents. Whole-exome libraries were prepared according to the Nimblegen SeqCap EZ Exome v3 protocol and sequencing was performed on NextSeq 500 for all of them. Furthermore, we performed in silico analysis of a virtual gene panel, focused on congenital neutropenias. Whole-exome sequencing identified a compound heterozygous genotype in SBDS gene in both siblings. We identified a likely pathogenic missense variant c.355T&gt;C; p.(Cys119Arg) in exon 3 of SBDS gene, leading to substitution of strongly conserved cysteine for arginine. This variant has been previously reported in a French family with SDS (Donadieu et al., 2012). Furthermore, we identified a rare, previously undescribed missense variant, c.536C&gt;T; p.(Pro179Leu), leading to prolin - leucine substitution. In-silico analysis (Align GVGD, SIFT, MutationTaster) predicts pathogenic or likely pathogenic effect. Molecular-genetic analysis of parents confirmed heterozygous carrier status. Compound heterozygous mutations in SBDS leads to disruption of SBDS gene and clinical manifestation of Shwachman-Diamond syndrome in the siblings.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

30205 - Hematology

Project

<a href="/en/project/NV16-29447A" target="_blank" >NV16-29447A: Searching for mutations predisposing to familial hematologic and oncologic diseases</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů