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

American Journal of Medical Genetics. Part a
Miroslava HancarovaZdenek Sedlacek

Abstract

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.

References

Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Sep 24, 2015·European Journal of Human Genetics : EJHG·Julia Lauer ZillhardtJamel Chelly
Dec 15, 2015·Nature Genetics·Raheleh RahbariMatthew E Hurles
Apr 14, 2016·Annual Review of Genomics and Human Genetics·Norman Arnheim, Peter Calabrese
Dec 13, 2016·Nature Reviews. Genetics·Lars A ForsbergJan P Dumanski
Jan 31, 2017·Nature·UNKNOWN Deciphering Developmental Disorders Study
Sep 5, 2017·American Journal of Human Genetics·Deidre R KruppBrian J O'Roak
Jun 14, 2018·Human Mutation·Manuela PrioloRaoul C Hennekam
Nov 7, 2018·Nature Genetics·Hákon JónssonKari Stefansson

❮ Previous
Next ❯

Citations

Sep 19, 2020·American Journal of Medical Genetics. Part a·Nydia Rena Benita SihombingSultana M H Faradz
Dec 25, 2019·Nature Medicine·Martin W BreussJoseph G Gleeson
Jun 24, 2021·Trends in Genetics : TIG·Martin W BreussJoseph G Gleeson

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

The New England Journal of Medicine
E ENGEL
Orvosi hetilap
D Schuler, G Gács
Acta Paediatrica Academiae Scientiarum Hungaricae
D Schuler, G Gács
© 2021 Meta ULC. All rights reserved