title: Exome sequencing expands the mechanism of SOX5-associated intellectual disability: A case presentation with review of sox-related disorders.
abstract: The SOX5 haploinsufficiency syndrome is characterized by global developmental delay, intellectual disability, language and motor impairment, and distinct facial features. The smallest deletion encompassed only one gene, SOX5 (OMIM 604975), indicating that haploinsufficiency of SOX5 contributes to neuro developmental delay. Although multiple deletions of the SOX5 gene have been reported in patients, none are strictly intragenic point mutations. Here, we report the identification of a de novo loss of function variant in SOX5 identified through whole exome sequencing. The proband presented with moderate developmental delay, bilateral optic atrophy, mildly dysmorphic features, and scoliosis, which correlates with the previously-described SOX5-associated phenotype. These results broaden the diagnostic spectrum of SOX5-related intellectual disability. Furthermore it highlights the utility of exome sequencing in establishing an etiological basis in clinically and genetically heterogeneous conditions such as intellectual disability.
authors.affiliation: Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Addie
authors.initials: A
authors.lastname: Nesbitt
authors.affiliation: Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Bhoj
authors.affiliation: Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Kristin
authors.initials: K
authors.lastname: McDonald Gibson
authors.affiliation: Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Denenberg
authors.affiliation: Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Sarmady
authors.affiliation: Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Tanya
authors.initials: T
authors.lastname: Tischler
authors.affiliation: Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Kajia
authors.initials: K
authors.lastname: Cao
authors.affiliation: Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Holly
authors.initials: H
authors.lastname: Dubbs
authors.affiliation: Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.affiliation: Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Department of Pathology and Laboratory Medicine, Molecular Genetics Laboratory, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Avni
authors.initials: A
authors.lastname: Santani
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D018389:Codon, Nonsense / Q000235:genetics; D059472:Exome / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008969:Molecular Sequence Data; D055755:SOXD Transcription Factors / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; C490301:SOX5 protein, human; D055755:SOXD Transcription Factors
keywords: 12p12; 12p12 microdeletion syndrome; SOX gene family; SOX5; SOX5-associated intellectual disability syndrome; SRY-BOX5; SRY-related HMG-box gene 5; intellectual disability; whole exome sequencing