Parental gonadal but not somatic mosaicism leading to de novo NFIX variants shared by two brothers with Malan syndrome

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F19%3A10396048" target="_blank" >RIV/00064203:_____/19:10396048 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/19:10396048 RIV/00216208:11130/19:10396048
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ne11NqPul5" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ne11NqPul5</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/ajmg.a.61302" target="_blank" >10.1002/ajmg.a.61302</a>

Result language
angličtina
Original language name
Parental gonadal but not somatic mosaicism leading to de novo NFIX variants shared by two brothers with Malan syndrome
Original language description
The importance of gonadal mosaicism in families with apparently de novo mutations is being increasingly recognized. We report on two affected brothers initially suggestive of X-linked or autosomal recessive inheritance. Malan syndrome due to shared NFIX variants was diagnosed in the brothers using exome sequencing. The boys shared the same paternal but not maternal haplotype around NFIX, and deep amplicon sequencing showed similar to 7% of the variant in paternal sperm but not in paternal blood and saliva. We performed review of previous cases of gonadal mosaicism, which suggests that the phenomenon is not uncommon. Gonadal mosaicism is often not accompanied by somatic mosaicism in tissues routinely used for testing, and if both types of mosaicism are present, the frequency of the variant in sperm is often higher than in somatic cells. In families with shared apparently de novo variants without evidence of parental somatic mosaicism, the transmitting parent may be determined through haplotyping of exome variants. Gonadal mosaicism has important consequences for recurrence risks and should be considered in genetic counseling in families with de novo variants.
Czech name
—
Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10600 - Biological sciences

Project
<a href="/en/project/NV17-29423A" target="_blank" >NV17-29423A: Analysis of genetic variants associated with intellectual disability and autism spectrum disorders using next generation sequencing</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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