title: A Nonsense Mutation in the Hedgehog Receptor CDON Associated With Pituitary Stalk Interruption Syndrome.
abstract: BACKGROUND
  Pituitary stalk interruption syndrome (PSIS) and holoprosencephaly (HPE) are congenital midline defects. Rare mutations in the sonic hedgehog (SHH) signaling gene CDON have recently been reported in patients with HPE.
  
  
  OBJECTIVE
  To report a unique case of PSIS with a maternally inherited nonsense mutation in the SHH signaling protein CDON.
  
  
  METHODS
  We performed exome sequencing on a case of PSIS. Control databases (1000 Genomes, dbSNP, Exome Variant Server, ExAC Browser) and an ancestry-matched control panel were screened upon identification of CDON mutation.
  
  
  RESULTS
  We identified a novel heterozygous nonsense mutation (c.2764T>C, Glu922Ter) in a case of PSIS without HPE who presented with neonatal hypoglycemia and cholestasis associated with GH, TSH, and ACTH deficiencies. This mutation was absent in all control databases and from 400 healthy ancestry-matched control subjects. The mutation was inherited from the patient's mother, who was operated on in childhood for strabismus. The absence of this variant in control samples suggests that it is likely to be responsible for the phenotype.
  
  
  CONCLUSIONS
  We report for the first time a mutation in the CDON gene associated with PSIS.
authors.affiliation: Human Developmental Genetics (A.B., J.B.-T., K.M.), Institut Pasteur, 75724 Paris, France; Institut Pasteur of Morocco (H.R.), 20100 Casablanca, Morocco; and Université Paris Descartes and Pediatric Endocrinology Unit (R.B.), Fondation Ophtalmologique Adolphe de Rothschild, 75019 Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Bashamboo
authors.affiliation: Human Developmental Genetics (A.B., J.B.-T., K.M.), Institut Pasteur, 75724 Paris, France; Institut Pasteur of Morocco (H.R.), 20100 Casablanca, Morocco; and Université Paris Descartes and Pediatric Endocrinology Unit (R.B.), Fondation Ophtalmologique Adolphe de Rothschild, 75019 Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Bignon-Topalovic
authors.affiliation: Human Developmental Genetics (A.B., J.B.-T., K.M.), Institut Pasteur, 75724 Paris, France; Institut Pasteur of Morocco (H.R.), 20100 Casablanca, Morocco; and Université Paris Descartes and Pediatric Endocrinology Unit (R.B.), Fondation Ophtalmologique Adolphe de Rothschild, 75019 Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Rouba
authors.affiliation: Human Developmental Genetics (A.B., J.B.-T., K.M.), Institut Pasteur, 75724 Paris, France; Institut Pasteur of Morocco (H.R.), 20100 Casablanca, Morocco; and Université Paris Descartes and Pediatric Endocrinology Unit (R.B.), Fondation Ophtalmologique Adolphe de Rothschild, 75019 Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: McElreavey
authors.affiliation: Human Developmental Genetics (A.B., J.B.-T., K.M.), Institut Pasteur, 75724 Paris, France; Institut Pasteur of Morocco (H.R.), 20100 Casablanca, Morocco; and Université Paris Descartes and Pediatric Endocrinology Unit (R.B.), Fondation Ophtalmologique Adolphe de Rothschild, 75019 Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Brauner
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000172:deficiency; D015815:Cell Adhesion Molecules / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics; D030541:Databases, Genetic; D005091:Exons / Q000235:genetics; D016142:Holoprosencephaly / Q000235:genetics; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010900:Pituitary Diseases / Q000235:genetics* / Q000473:pathology*; D010902:Pituitary Gland / Q000473:pathology*; D013577:Syndrome; D013972:Thyrotropin / Q000172:deficiency; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C107286:CDON protein, human; D015815:Cell Adhesion Molecules; D018389:Codon, Nonsense; D025521:Tumor Suppressor Proteins; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D013972:Thyrotropin