Coffin-Siris syndrome: phenotypic evolution of a novel SMARCA4 mutation.
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.
NIH Undiagnosed Diseases Program, Common Fund, NIH Office of the Director and NHGRI, Bethesda, Maryland.
Michael
M
Tzeng
Christèle
C
du Souich
Helen Wing-Hong
HW
Cheung
Cornelius F
CF
Boerkoel
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001921:Brain / Q000473:pathology; D002648:Child; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005145:Face / Q000002:abnormalities*; D019066:Facies; D056726:Genetic Association Studies; D056426:Genetic Loci; D006228:Hand Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008844:Micrognathism / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D009333:Neck / Q000002:abnormalities*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D010641:Phenotype; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases
choanal stenosis; chromatin remodeling; expressivity; intellectual disability; scoliosis