Parental gonadal but not somatic mosaicism leading to de novo NFIX variants shared by two brothers with Malan syndrome.
NFIX
Malan syndrome
de novo recurrence
gonadal mosaicism
somatic mosaicism
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
23
04
2019
revised:
02
07
2019
accepted:
09
07
2019
pubmed:
2
8
2019
medline:
4
8
2020
entrez:
2
8
2019
Statut:
ppublish
Résumé
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 ~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.
Identifiants
pubmed: 31369202
doi: 10.1002/ajmg.a.61302
doi:
Substances chimiques
NFI Transcription Factors
0
NFIX protein, human
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2119-2123Subventions
Organisme : Czech Ministry of Health
ID : 17-29423A
Pays : International
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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