Summary Statistics:
Gene Score: S
Relevance to Autism
Mutations in the SMC1A gene are responsible for a form of Cornelia de Lange syndrome (Cornelia de Lange syndrome 2; OMIM 300590), a clinically heterogeneous developmental disorder characterized by malformations affecting multiple systems (Deardorff et al., 2007). Phenotypic characterization of 51 individuals with SMC1A variants demonstrated that 6/6 individuals displayed socialization deficits (ranging from mild to profound) and 20/31 individuals (65%) exhibited stereotypic movements (Huisman et al., 2017); furthermore, 5 females from a cohort of 13 Dutch individuals with SMC1A variants presented with a phenotype similar to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability, stereotypic movements, and, in some cases, developmental regression.
Molecular Function
The cohesin multiprotein complex is required for sister chromatid cohesion, a prerequisite for the correct segregation of chromosomes during cell division, and is composed partly of two structural maintenance of chromosomes (SMC) proteins: SMC3 and either SMC1B or the protein encoded by this gene. Most of the cohesin complexes dissociate from the chromosomes before mitosis, although those complexes at the kinetochore remain. Therefore, the encoded protein is thought to be an important part of functional kinetochores.
References
Primary
Phenotypes and genotypes in individuals with SMC1A variants.
Cornelia de Lange syndrome-2 (CDLS2)
Support
ID, epilepsy/seizures
Support
Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study
DD, epilepsy/seizures
Support
Integrating de novo and inherited variants in 42
ASD
Support
De novo variants in neurodevelopmental disorders-experiences from a tertiary care center
DD, epilepsy/seizures
Support
Genetic and Phenotype Analysis of a Chinese Cohort of Infants and Children With Epilepsy
Epilepsy/seizures
DD, ID
Support
Trio-whole exome sequencing reveals the importance of de novo variants in children with intellectual disability and developmental delay
DD/ID, epilepsy/seizures
Support
Exploring the biological role of postzygotic and germinal de novo mutations in ASD
ASD
Support
Genetic analysis using targeted exome sequencing of 53 Vietnamese children with developmental and epileptic encephalopathies
DD, epilepsy/seizures
Support
Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings
DD, ID, epilepsy/seizures
Support
Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.
ASD, epilepsy/seizures
Support
Trio-based exome sequencing reveals a high rate of the de novo variants in intellectual disability
ID
Support
Whole Exome Sequencing as a First-Line Molecular Genetic Test in Developmental and Epileptic Encephalopathies
ID, epilepsy/seizures
Support
Clinical genome sequencing in an unbiased pediatric cohort.
Cornelia de Lange syndrome-2 (CDLS2)
DD, epilepsy/seizures, microcephaly
Support
Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders
ID
Support
Clinical Utility of Proband Only Clinical Exome Sequencing in Neurodevelopmental Disorders
ASD, DD, ID, epilepsy/seizures
Support
Cornelia de Lange syndrome mutations in SMC1A or SMC3 affect binding to DNA.
Support
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies
DD, ID
ADHD, epilepsy/seizures
Highly Cited
Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation.
Cornelia de Lange syndrome-2 (CDLS2)
Recent Recommendation
Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement.
Cornelia de Lange syndrome-2 (CDLS2)
GEN913R001
inframe_deletion
c.107del
p.Val36GlufsTer7
De novo
GEN913R002
missense_variant
c.397T>G
p.Phe133Val
De novo
GEN913R003
missense_variant
c.587G>A
p.Arg196His
De novo
GEN913R004
missense_variant
c.1486C>T
p.Arg496Cys
Familial
Maternal
Multiplex
GEN913R005
missense_variant
c.1421G>A
p.Arg474His
Familial
Multiplex
GEN913R006
missense_variant
c.1487G>A
p.Arg496His
De novo (germline mosaicism)
Multiplex
GEN913R007
missense_variant
c.1487G>A
p.Arg496His
Unknown
GEN913R008
missense_variant
c.2131C>T
p.Arg711Trp
De novo
GEN913R009
missense_variant
c.2369G>A
p.Arg790Gln
De novo
GEN913R010
missense_variant
c.3364T>C
p.Phe1122Leu
De novo
GEN913R011
missense_variant
c.31A>T
p.Asn11Tyr
Unknown
GEN913R012
frameshift_variant
c.157dup
p.Thr53AsnfsTer34
Unknown
GEN913R013
stop_gained
c.694G>T
p.Glu232Ter
Unknown
GEN913R014
frameshift_variant
c.2364del
p.Asn788LysfsTer10
Unknown
GEN913R015
frameshift_variant
c.2357del
p.Leu786TrpfsTer21
Unknown
GEN913R016
stop_gained
c.52C>T
p.Arg18Ter
Familial
Maternal
GEN913R017
missense_variant
c.3617A>T
p.Glu1206Val
Unknown
Simplex
GEN913R018
missense_variant
c.2369G>A
p.Arg790Gln
De novo
Simplex
GEN913R019
missense_variant
c.587G>C
p.Arg196Pro
De novo
Unknown
GEN913R020
missense_variant
c.3497A>C
p.Asn1166Thr
De novo
Unknown
GEN913R021
frameshift_variant
c.2364_2379del
p.Asn788LysfsTer5
Unknown
GEN913R022
missense_variant
c.2341T>C
p.Cys781Arg
De novo
Simplex
GEN913R023
stop_gained
c.1171C>T
p.Gln391Ter
De novo
Simplex
GEN913R024
inframe_deletion
c.802_804del
p.Lys268del
De novo
Simplex
GEN913R025
missense_variant
c.1405C>T
p.Arg469Cys
Familial
Maternal
GEN913R026
missense_variant
c.2095C>T
p.Arg699Cys
De novo
GEN913R027
stop_gained
c.358G>T
p.Glu120Ter
De novo
Simplex
GEN913R028
missense_variant
c.607A>G
p.Lys203Glu
De novo
Simplex
GEN913R029
missense_variant
c.1903C>T
p.Arg635Cys
De novo
GEN913R030
stop_gained
c.3103C>T
p.Arg1035Ter
De novo
Simplex
GEN913R031
splice_site_variant
c.3219+1G>C
De novo
Simplex
GEN913R032
inframe_deletion
c.261_263del
p.Asn87del
De novo
Simplex
GEN913R033
stop_gained
c.547C>T
p.Gln183Ter
Unknown
GEN913R034
frameshift_variant
c.611_612del
p.Glu204GlyfsTer3
De novo
GEN913R035
stop_gained
c.1192C>T
p.Arg398Ter
Unknown
GEN913R036
stop_gained
c.511C>T
p.Arg171Ter
De novo
Simplex
GEN913R037
missense_variant
c.562C>T
p.Arg188Cys
De novo
Simplex
GEN913R038
frameshift_variant
c.138_139insA
p.Phe47IlefsTer5
De novo
Simplex
No Common Variants Available
X
Deletion-Duplication
27
X
Deletion-Duplication
22
No Interactions Available
