Abstract
Deleterious variants in the transcription factor early B-cell factor 3 (EBF3) are known to cause a neurodevelopmental disorder (EBF3-NDD). We report eleven individuals with EBF3 variants, including an individual with a duplication/triplication mosaicism of a region encompassing EBF3 and a phenotype consistent with EBF3-NDD, which may reflect the importance of EBF3 gene-dosage for neurodevelopment. The phenotype of individuals in this cohort was quite mild compared to the core phenotype of previously described individuals. Although ataxia tended to wane with age, we show that cognitive difficulties may increase, and we recommend that individuals with EBF3-NDD have systematic neuropsychological follow-up.
Highlights
Heterozygous variants in the transcription factor early B-cell factor 3 (EBF3) are reported to cause a neurodevelopmental disorder which is called hypotonia, ataxia and delayed development syndrome (HADDS)conserved EBF- transcription factor family, members of which have a variety of developmental roles 4
Ataxia tended to wane with age, we show that cognitive difficulties may increase, and we recommend that individuals with EBF3-NDD have systematic neuropsychological follow-up
We identified a duplication/triplication mosaicism of the EBF3 gene as a possible genetic mechanism in EBF3-related disease
Summary
Heterozygous variants in the transcription factor early B-cell factor 3 (EBF3) are reported to cause a neurodevelopmental disorder which is called hypotonia, ataxia and delayed development syndrome (HADDS)conserved EBF- transcription factor family, members of which have a variety of developmental roles 4. Heterozygous variants in the transcription factor early B-cell factor 3 (EBF3) are reported to cause a neurodevelopmental disorder which is called hypotonia, ataxia and delayed development syndrome (HADDS). Retzius-cells estimated that pathogenic EBF3 variants could be the underlying cause in 1:1000 individuals with unexplained neurodevelopmental disorders neurodevelopmental disorder (EBF3-NDD) is likely vastly underdiagnosed. Growing number of individuals are described [1,2,3, 5, 7,8,9,10,11,12,13,14], the EBF3-associated phenotype is expanding and new disease features continue to be reported. EBF3-haploinsufficiency is reported to be a likely pathogenic mechanism for EBF3-NDD. In individuals with EBF3-NDD most reported variants are de novo missense or nonsense variants, but other variant types, such as deletions, have been reported.
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