Mutations in STAG2 cause an X-linked cohesinopathy associated with undergrowth, developmental delay, and dysmorphia: Expanding the phenotype in males.
STAG2
X-linked gene
clinical exome sequencing
cohesin complex
cohesin-associated genes
cohesinopathies
human growth
neurodevelopment
reanalysis
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
22
06
2018
revised:
27
09
2018
accepted:
10
10
2018
pubmed:
18
11
2018
medline:
12
4
2019
entrez:
18
11
2018
Statut:
ppublish
Résumé
The cohesin complex is a multi-subunit protein complex which regulates sister chromatid cohesion and separation during cellular division. In addition, this evolutionarily conserved protein complex plays an integral role in DNA replication, DNA repair, and the regulation of transcription. The core complex is composed of four subunits: RAD21, SMC1A, SMC3, and STAG1/2. Mutations in these proteins have been implicated in human developmental disorders collectively termed "cohesinopathies." Using clinical exome sequencing, we have previously identified three female cases with heterozygous STAG2 mutations and overlapping syndromic phenotypes. Subsequently, a familial missense variant was identified in five male family members. We now present the case of a 4-year-old male with developmental delay, failure to thrive, short stature, and polydactyly with a likely pathogenic STAG2 de novo missense hemizygous variant, c.3027A>T, p.Lys1009Asn. Furthermore, we compare the phenotypes of the four previously reported STAG2 variants with our case. We conclude that mutations in STAG2 cause a novel constellation of sex-specific cohesinopathy-related phenotypes and are furthermore, essential for neurodevelopment, human growth, and behavioral development.
Sections du résumé
BACKGROUND
The cohesin complex is a multi-subunit protein complex which regulates sister chromatid cohesion and separation during cellular division. In addition, this evolutionarily conserved protein complex plays an integral role in DNA replication, DNA repair, and the regulation of transcription. The core complex is composed of four subunits: RAD21, SMC1A, SMC3, and STAG1/2. Mutations in these proteins have been implicated in human developmental disorders collectively termed "cohesinopathies."
METHODS
Using clinical exome sequencing, we have previously identified three female cases with heterozygous STAG2 mutations and overlapping syndromic phenotypes. Subsequently, a familial missense variant was identified in five male family members.
RESULTS
We now present the case of a 4-year-old male with developmental delay, failure to thrive, short stature, and polydactyly with a likely pathogenic STAG2 de novo missense hemizygous variant, c.3027A>T, p.Lys1009Asn. Furthermore, we compare the phenotypes of the four previously reported STAG2 variants with our case.
CONCLUSION
We conclude that mutations in STAG2 cause a novel constellation of sex-specific cohesinopathy-related phenotypes and are furthermore, essential for neurodevelopment, human growth, and behavioral development.
Identifiants
pubmed: 30447054
doi: 10.1002/mgg3.501
pmc: PMC6393687
doi:
Substances chimiques
Antigens, Nuclear
0
Cell Cycle Proteins
0
STAG2 protein, human
0
Banques de données
GENBANK
['NC_000023.10']
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00501Subventions
Organisme : NICHD NIH HHS
ID : U54 HD090257
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD055784
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000124
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008042
Pays : United States
Informations de copyright
© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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