title: Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features.
abstract: SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system. Despite its important developmental roles, SOX5 disruption has yet to be associated with human disease. We report one individual with a reciprocal translocation breakpoint within SOX5, eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent), and seven individuals with larger 12p12 deletions encompassing SOX5. Common features in these subjects include prominent speech delay, intellectual disability, behavior abnormalities, and dysmorphic features. The phenotypic impact of the deletions may depend on the location of the deletion and, consequently, which of the three major SOX5 protein isoforms are affected. One intragenic deletion, involving only untranslated exons, was present in a more mildly affected subject, was inherited from a healthy parent and grandparent, and is similar to a deletion found in a control cohort. Therefore, some intragenic SOX5 deletions may have minimal phenotypic effect. Based on the location of the deletions in the subjects compared to the controls, the de novo nature of most of these deletions, and the phenotypic similarities among cases, SOX5 appears to be a dosage-sensitive, developmentally important gene.
authors.affiliation: Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, Washington 99207, USA.
authors.forename: Allen N
authors.initials: AN
authors.lastname: Lamb
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rosenfeld
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Neill
authors.forename: Michael E
authors.initials: ME
authors.lastname: Talkowski
authors.forename: Ian
authors.initials: I
authors.lastname: Blumenthal
authors.forename: Santhosh
authors.initials: S
authors.lastname: Girirajan
authors.forename: Debra
authors.initials: D
authors.lastname: Keelean-Fuller
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fan
authors.forename: Jill
authors.initials: J
authors.lastname: Pouncey
authors.forename: Cathy
authors.initials: C
authors.lastname: Stevens
authors.forename: Loren
authors.initials: L
authors.lastname: Mackay-Loder
authors.forename: Deborah
authors.initials: D
authors.lastname: Terespolsky
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Bader
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rosenbaum
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Vallee
authors.forename: John B
authors.initials: JB
authors.lastname: Moeschler
authors.forename: Roger
authors.initials: R
authors.lastname: Ladda
authors.forename: Susan
authors.initials: S
authors.lastname: Sell
authors.forename: Judith
authors.initials: J
authors.lastname: Martin
authors.forename: Shawnia
authors.initials: S
authors.lastname: Ryan
authors.forename: Marilyn C
authors.initials: MC
authors.lastname: Jones
authors.forename: Rocio
authors.initials: R
authors.lastname: Moran
authors.forename: Amy
authors.initials: A
authors.lastname: Shealy
authors.forename: Suneeta
authors.initials: S
authors.lastname: Madan-Khetarpal
authors.forename: Juliann
authors.initials: J
authors.lastname: McConnell
authors.forename: Urvashi
authors.initials: U
authors.lastname: Surti
authors.forename: Andrée
authors.initials: A
authors.lastname: Delahaye
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Heron-Longe
authors.forename: Eva
authors.initials: E
authors.lastname: Pipiras
authors.forename: Brigitte
authors.initials: B
authors.lastname: Benzacken
authors.forename: Sandrine
authors.initials: S
authors.lastname: Passemard
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.forename: Cedric
authors.initials: C
authors.lastname: Le Caignec
authors.forename: Gwen M
authors.initials: GM
authors.lastname: Glew
authors.forename: Kent E
authors.initials: KE
authors.lastname: Opheim
authors.forename: Maria
authors.initials: M
authors.lastname: Descartes
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Morton
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Roger A
authors.initials: RA
authors.lastname: Schultz
authors.forename: Blake C
authors.initials: BC
authors.lastname: Ballif
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
mesh_terms: D000293:Adolescent; D000328:Adult; D057215:Body Dysmorphic Disorders / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D057895:Haploinsufficiency; D006801:Humans; D007805:Language Development Disorders / Q000235:genetics*; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D055755:SOXD Transcription Factors / Q000235:genetics*
chemical_list: C490301:SOX5 protein, human; D055755:SOXD Transcription Factors