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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11110/19:10396048 RIV/00216208:11130/19:10396048

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10600 - Biological sciences

Projekt

<a href="/cs/project/NV17-29423A" target="_blank" >NV17-29423A: Analýza genetických variant asociovaných s mentální retardaci a poruchami autistického spektra s využitím sekvenování nové generace</a><br>

Návaznosti

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

American Journal of Medical Genetics: Part A

ISSN

1552-4825

e-ISSN

—

Svazek periodika

179

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

5

Strana od-do

2119-2123

Kód UT WoS článku

000479905700001

EID výsledku v databázi Scopus

2-s2.0-85070060775