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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.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Phenotypes and genotypes in individuals with SMC1A variants.
Cornelia de Lange syndrome-2 (CDLS2)
Support
De novo variants in neurodevelopmental disorders-experiences from a tertiary care center
DD, epilepsy/seizures
Support
Exploring the biological role of postzygotic and germinal de novo mutations in ASD
ASD
Support
Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.
ASD, epilepsy/seizures
Support
Clinical genome sequencing in an unbiased pediatric cohort.
Cornelia de Lange syndrome-2 (CDLS2)
DD, epilepsy/seizures, microcephaly
Support
Cornelia de Lange syndrome mutations in SMC1A or SMC3 affect binding to DNA.
Support
Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study
DD, 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)

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN913R001 
 inframe_deletion 
 c.107del 
 p.Val36GlufsTer7 
 De novo 
 NA 
  
 GEN913R002 
 missense_variant 
 c.397T>G 
 p.Phe133Val 
 De novo 
 NA 
  
 GEN913R003 
 missense_variant 
 c.587G>A 
 p.Arg196His 
 De novo 
 NA 
  
 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 
 NA 
  
 GEN913R009 
 missense_variant 
 c.2369G>A 
 p.Arg790Gln 
 De novo 
 NA 
  
 GEN913R010 
 missense_variant 
 c.3364T>C 
 p.Phe1122Leu 
 De novo 
 NA 
  
 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 
 NA 
 Simplex 
 GEN913R019 
 missense_variant 
 c.587G>C 
 p.Arg196Pro 
 De novo 
 NA 
 Unknown 
 GEN913R020 
 missense_variant 
 c.3497A>C 
 p.Asn1166Thr 
 De novo 
 NA 
 Unknown 
 GEN913R021 
 frameshift_variant 
 c.2364_2379del 
 p.Asn788LysfsTer5 
 Unknown 
  
  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
X
Deletion-Duplication
 24
 
X
Duplication
 1
 
X
Duplication
 1
 
X
Duplication
 1
 
X
Deletion
 1
 
X
Deletion
 4
 
X
Deletion-Duplication
 1
 
X
Deletion
 1
 
X
Deletion-Duplication
 18
 

No Animal Model Data Available

 

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