This report describes Coffin-Siris syndrome 11 (CSS11), a syndromic neurodevelopmental disorder caused by mutations in the human gene SMARCD1, a member of the SWI/SNF family of chromatin remodeling complexes. CSS11 shows autosomal dominant inheritance. Multiple genes within the SWI/SNF family have been implicated in the form of syndromic intellectual disability designated Coffin-Siris syndrome; OMIM also classifies these diseases under the phenotypic series for autosomal dominant intellectual disability (see FBhh0000127).
There is a single high-ranking ortholog of SMARCD1 in Drosophila, Bap60. Dmel\Bap60 is also orthologous to two related genes in human, SMARCD2 and SMARCD3. Several alleles of Bap60 have been generated, including RNAi targeting constructs and insertions.
The human gene SMARCD1 has not been introduced into flies.
Multiple loss-of-function alleles of Bap60 are lethal at different stages of development. Knocking down Bap60 in the mushroom body (a brain region associated with learning and memory) causes male flies not to reduce courtship attempts after being rejected by a female, a measure of memory formation in flies. Both short-term and long-term memory impairment are observed. Defects in mushroom body morphology are observed, including defects in pruning of the MBγ neurons during pupal morphogenesis.
[updated Mar. 2020 by FlyBase; FBrf0222196]
Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).
Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).
Coffin-Siris syndrome is a multiple malformation syndrome characterized by mental retardation associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other more variable features may include poor overall growth, craniofacial abnormalities, spinal anomalies, and congenital heart defects (review by Vergano and Deardorff, 2014; pubmed:25169447). [from MIM:135900; 2019.07.19]
Coffin-Siris syndrome is a multiple malformation syndrome characterized by intellectual disability associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other more variable features may include poor overall growth, craniofacial abnormalities, spinal anomalies, and congenital heart defects (review by Vergano and Deardorff, 2014; pubmed:25169447). [from MIM:135900; 2019.07.19]
[COFFIN-SIRIS SYNDROME 11; CSS11](https://omim.org/entry/618779)
[SWI/SNF-RELATED, MATRIX-ASSOCIATED, ACTIN-DEPENDENT REGULATOR OF CHROMATIN, SUBFAMILY D, MEMBER 1; SMARCD1](https://omim.org/entry/601735)
Five individuals who presented with developmental delay, intellectual disability, hypotonia, feeding difficulties, and small hands and feet were found to have mutations in SMARCD1. (Nixon et al. 2019, FBrf0241961)
Coffin-Siris syndrome-11 (CSS11) is caused by heterozygous mutation in the SMARCD1 gene. [from MIM:618779; 2020.03.02]
Mutations in SMARCD1 seen in five affected individuals were clustered in the C terminus of the protein, and did not disrupt the association of SMARCD1 with SMARCA4 or SMARCC1. (Nixon et al. 2019, FBrf0241961) SMARCD1 is part of the core of the BRG1/BRM-associated factor (BAF) class of SWI/SNF chromatin remodeling complexes, along with dimers (both homo- and heterodimers) of SMARCC1 and SMARCC2. (Mashtalir et al. 2018, FBrf0240696)
Many to one: 3 human to 1 Drosophila.
High-scoring ortholog of human SMARCD1, SMARCD2, SMARCD3 (1 Drosophila to 3 human). Dmel\Bap60 shares 55-64% identity and 66-72% similarity with the human genes.
