This report describes neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, an intellectual developmental disorder that exhibits autosomal dominant inheritance. The human gene implicated is SUPT16H, which encodes a member of the FACT (facilitates chromatin transcription) complex. There is one high-scoring fly ortholog, Dmel\dre4, for which a loss-of-function allele and RNAi-targeting constructs have been generated.
UAS constructs of the human Hsap\SUPT16H, gene, including wild-type SUPT16H and variants implicated in disease (T171I, G808R), have been introduced into flies. See the 'Disease-Implicated Variants' table below. Overexpression of wild-type or variant human SUPT16H in a wild-type Dmel\dre4 does not result in a phenotype, nor rescue lethality for Dmel\dre loss-of-function mutants. However, partial heterologous rescue (functional complementation) is observed for phenotypes resulting from tissue-specific RNAi knockdown for Dmel\dre4.
Flies homozygous for loss-of-function alleles of Dmel\dre4, or ubiquitous knockdown with an RNAi construct, typically die during the first or second instar. Tissue-specific RNAi knockdown results in severe tissue-specific phenotypes which can be partially rescued by expression of wild-type Hsap\SUPT16H; coexpression of disease-implicated variants show very limited rescue in affected tissues.
[updated Apr. 2024 by FlyBase; FBrf0222196]
[NEURODEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND THIN CORPUS CALLOSUM; NEDDFAC](https://omim.org/entry/619480)
[SPT16 HOMOLOG, FACILITATES CHROMATIN REMODELING SUBUNIT; SUPT16H](https://omim.org/entry/605012)
Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum (NEDDFAC) is characterized by global developmental delay, impaired intellectual development with poor or absent speech and language, and dysmorphic facial features. Brain imaging tends to show thin corpus callosum and decreased white matter volume. Additional features such as seizures, cardiac defects, and behavioral abnormalities may also occur. The phenotype is variable (summary by Bina et al., 2020, pubmed:31924697). [from MIM:619480; 2023.03.21]
Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum (NEDDFAC) is caused by heterozygous mutation in the SUPT16H gene (605012) on chromosome 14q11. [from MIM:619480; 2023.03.21]
The SUPT16H gene encodes a component of the FACT (facilitates chromatin transcription) complex, a chromatin-specific factor required for transcription elongation as well as for DNA replication and repair (summary by Belotserkovskaya et al., 2003, pubmed:12934006). [from MIM:605012; 2023.03.21]
One to one (1 human to 1 Drosophila); SUPT16H has one high-scoring Drosophila ortholog, dre4.
High-scoring ortholog of human SUPT16H (1 Drosophila to 1 human).
