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

Kód výsledku v 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>

Výsledek na webu

<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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Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30205 - Hematology

Projekt

<a href="/cs/project/NV16-29447A" target="_blank" >NV16-29447A: Vyhledávání mutací predisponujících k familiárním hematologickým a onkologickým onemocněním</a><br>

Návaznosti

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

Rok uplatnění

2020

Kód důvěrnosti údajů

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