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Null variants in AGRN cause lethal fetal akinesia deformation sequence
Author(s) -
Geremek Maciej,
Dudarewicz Lech,
Obersztyn Ewa,
Paczkowska Magdalena,
Smyk Marta,
Sobecka Katarzyna,
Nowakowska Beata
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13677
Subject(s) - frameshift mutation , genetics , biology , exon , gene , phenotype , sequence (biology)
We present a case of lethal fetal akinesia deformation sequence (FADS) caused by a frameshift variant in trans with a 148 kbp deletion encompassing 3‐36 exons of AGRN . Pathogenic variants in AGRN have been described in families with a form of congenital myasthenic syndrome (CMS), manifesting in the early childhood with variable fatigable muscle weakness. To the best of our knowledge, this is the first case of FADS caused by defects in AGRN gene. FADS has been reported to be caused by pathogenic variants in genes previously associated with CMS including these involved in endplate development and maintenance: MuSK , DOK7 , and RAPSN . FADS seems to be the most severe form of CMS. None of the reported in the literature CMS cases associated with AGRN had two null variants, like the case presented herein. This indicates a strong genotype‐phenotype correlation.