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Coffin‐Siris syndrome: Phenotypic evolution of a novel SMARCA4 mutation
Author(s) -
Tzeng Michael,
du Souich Christèle,
Cheung Helen WingHong,
Boerkoel Cornelius F.
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36533
Subject(s) - missense mutation , smarca4 , phenotype , genetics , mutation , exon , biology , intellectual disability , medicine , chromatin , chromatin remodeling , gene
Coffin‐Siris Syndrome (CSS) is an intellectual disability disorder caused by mutation of components of the SWI/SNF chromatin‐remodeling complex. We describe the evolution of the phenotypic features for a male patient with CSS from birth to age 7 years and 9 months and by review of reported CSS patients, we expand the phenotype to include neonatal and infantile hypertonia and upper airway obstruction. The propositus had a novel de novo heterozygous missense mutation in exon 17 of SMARCA4 (NM_001128849.1:c.2434C>T (NP_001122321.1:p.Leu812Phe)). This is the first reported mutation within motif Ia of the SMARCA4 SNF2 domain. In summary, SMARCA4 ‐associated CSS is a pleiotropic disorder in which the pathognomic clinical features evolve and for which the few reported individuals do not demonstrate a clear genotype–phenotype correlation. © 2014 Wiley Periodicals, Inc.