PuSH - Publication Server of Helmholtz Zentrum München: Biallelic loss-of-function variants of <em>ZFTRAF1</em> cause neurodevelopmental disorder with microcephaly and hypotonia.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Asif, M.* ; Khayyat, A.I.A.* ; Alawbathani, S.* ; Abdullah, U.* ; Sanner, A.* ; Georgomanolis, T.* ; Haasters, J.* ; Becker, K.* ; Budde, B.* ; Becker, C.* ; Thiele, H.* ; Baig, S.M.* ; Isidoro-García, M.* ; Winter, D.* ; Pogoda, H.M.* ; Muhammad, S.* ; Hammerschmidt, M.* ; Kraft, F.* ; Kurth, I.* ; Martin, H.G.* ; Wagner, M. ; Nürnberg, P.* ; Hussain, M.S.*

Biallelic loss-of-function variants of ZFTRAF1 cause neurodevelopmental disorder with microcephaly and hypotonia.

Genet. Med. 26:101143 (2024)

Publ. Version/Full Text

DOI

PMC

	Open Access Hybrid

Abstract
Metrics
Extra information

PURPOSE: Neurodevelopmental disorders exhibit clinical and genetic heterogeneity, ergo manifest dysfunction in components of diverse cellular pathways; the precise pathomechanism for the majority remains elusive. METHODS: We studied five affected individuals from three unrelated families manifesting global developmental delay, postnatal microcephaly, and hypotonia. We employed exome sequencing and prioritized variants that were subsequently characterized using immunofluorescence, immunoblotting, pulldown assays, and RNA sequencing. RESULTS: We identified biallelic variants in ZFTRAF1, encoding a protein of yet unknown function. Four affected individuals from two unrelated families segregated two homozygous frameshift variants in ZFTRAF1, whereas, in the third family, an intronic splice site variant was detected. We investigated ZFTRAF1 at the cellular level and signified it as a nucleocytoplasmic protein in different human cell lines. ZFTRAF1 was completely absent in the fibroblasts of two affected individuals. We also identified 110 interacting proteins enriched in mRNA processing and autophagy-related pathways. Based on profiling of autophagy markers, patient-derived fibroblasts show irregularities in the protein degradation process. CONCLUSION: Thus, our findings suggest that biallelic variants of ZFTRAF1 cause a severe neurodevelopmental disorder.

Impact Factor

Scopus SNIP

Altmetric

6.700

0.000