Coffin-Siris syndrome: phenotypic evolution of a novel SMARCA4 mutation.

Abstract

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.

• Authors: Michael Tzeng, Christèle du Souich, Helen Wing-Hong Cheung, Cornelius F Boerkoel
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 164A Issue 7 Pg. 1808-14 (Jul 2014) ISSN: 1552-4833 [Electronic] United States
• PMID: 24700502 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Nuclear Proteins
• Transcription Factors
• SMARCA4 protein, human
• DNA Helicases

Topics

• Abnormalities, Multiple (diagnosis, genetics)
• Amino Acid Sequence
• Amino Acid Substitution
• Brain (pathology)
• Child
• DNA Helicases (chemistry, genetics)
• DNA Mutational Analysis
• Face (abnormalities)
• Facies
• Genetic Association Studies
• Genetic Loci
• Hand Deformities, Congenital (diagnosis, genetics)
• Humans
• Intellectual Disability (diagnosis, genetics)
• Magnetic Resonance Imaging
• Male
• Micrognathism (diagnosis, genetics)
• Mutation
• Neck (abnormalities)
• Nuclear Proteins (chemistry, genetics)
• Phenotype
• Transcription Factors (chemistry, genetics)