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Expanding the clinical spectrum of biallelic ZNF335 variants
Author(s) -
Stouffs K.,
Stergachis A.B.,
Vanderhasselt T.,
Dica A.,
Janssens S.,
Vandervore L.,
Gheldof A.,
Bodamer O.,
Keymolen K.,
Seneca S.,
Liebaers I.,
Jayaraman D.,
Hill H.E.,
Partlow J.N.,
Walsh C.A.,
Jansen A.C.
Publication year - 2018
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.13260
Subject(s) - microcephaly , compound heterozygosity , hypoplasia , genetics , phenotype , brainstem , biology , cerebellar hypoplasia (non human) , cerebellum , neuroscience , anatomy , gene
ZNF335 plays an essential role in neurogenesis and biallelic variants in ZNF335 have been identified as the cause of severe primary autosomal recessive microcephaly in 2 unrelated families. We describe, herein, 2 additional affected individuals with biallelic ZNF335 variants, 1 individual with a homozygous c.1399 T > C, p.(Cys467Arg) variant, and a second individual with compound heterozygous c.2171_2173delTCT, p.(Phe724del) and c.3998A > G, p.(Glu1333Gly) variants with the latter variant predicted to affect splicing. Whereas the first case presented with early death and a severe phenotype characterized by anterior agyria with prominent extra‐axial spaces, absent basal ganglia, and hypoplasia of the brainstem and cerebellum, the second case had a milder clinical presentation with hypomyelination and otherwise preserved brain structures on MRI. Our findings expand the clinical spectrum of ZNF335 ‐associated microcephaly.