SMARCE1, a rare cause of Coffin-Siris Syndrome: Clinical description of three additional cases.
Coffin-Siris syndrome (CSS, MIM 135900), is a well-described, multiple congenital anomaly syndrome characterized by coarse facial features, hypertrichosis, sparse scalp hair, and hypo/aplastic digital nails and phalanges, typically of the 5th digits. Mutations in the BAF (SWI/SNF)-complex subunits (SMARCA4, SMARCE1, SMARCB1, SMARCA2, ARID1B, and ARID1A) have been shown to cause not only CSS, but also related disorders including Nicolaides-Baraitser (MIM 601358) syndrome and ARID1B-intellectual disability syndrome (MIM 614562). At least 200 individuals with CSS have been found to have a mutation in the BAF pathway. However, to date, only three individuals with CSS have been reported to have pathogenic variants in SMARCE1. We report here three additional individuals with clinical features consistent with CSS and alterations in SMARCE1, one of which is novel. The probands all exhibited dysmorphic facial features, moderate developmental and cognitive delay, poor growth, and hypoplastic digital nails/phalanges, including digits not typically affected in the other genes associated with CSS. Two of the three probands had a variety of different organ system anomalies, including cardiac disease, genitourinary abnormalities, feeding difficulties, and vision abnormalities. The 3rd proband has not had further investigative studies. Although an increasing number of individuals are being diagnosed with disorders in the BAF pathway, SMARCE1 is the least common of these genes. This report doubles the number of probands with these mutations, and allows for better phenotypic information of this rare syndrome. © 2016 Wiley Periodicals, Inc.
Section of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Yuri A
YA
Zarate
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Elizabeth
E
Bhoj
Section of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Julie
J
Kaylor
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Dong
D
Li
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yoshinori
Y
Tsurusaki
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Noriko
N
Miyake
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Naomichi
N
Matsumoto
Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Science, Lucknow, India.
Shubha
S
Phadke
Medical Genetics and Neurodevelopmental Pediatrics, St. Vincent's Peyton Manning Children's Hospital, Indianapolis, Indiana.
Luis
L
Escobar
Medical Genetics and Neurodevelopmental Pediatrics, St. Vincent's Peyton Manning Children's Hospital, Indianapolis, Indiana.
Afifa
A
Irani
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Hakon
H
Hakonarson
Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia.
Samantha A
SA
Schrier Vergano
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D059472:Exome; D005091:Exons; D005145:Face / Q000002:abnormalities*; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006228:Hand Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008844:Micrognathism / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D009333:Neck / Q000002:abnormalities*; D010641:Phenotype
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C504738:SMARCE1 protein, human
BAF-complex; Coffin-Siris syndrome; SMARCE1; exome sequencing