title: Three unrelated patients with congenital anterior pituitary aplasia and a characteristic physical and neuropsychological phenotype: a new syndrome?
abstract: Anterior pituitary aplasia (APA) is a very rare cause of congenital-onset multiple pituitary hormone deficiency (CO-MPHD). We report on molecular analysis and clinical follow-up of three previously reported cases of APA [Scommegna et al., 2004], who share a characteristic physical and neuropsychological profile. Mutation analysis of genes encoding transcription factors involved in pituitary development (PROP1, POUF1, HESX1, LHX3, and LHX4) did not demonstrate a any mutation. In order to identify the genetic cause underlying the phenotypes we performed an array-based comparative genomic hybridization (array-CGH), which showed a cryptic interstitial deletion of 9p (200 kb), including the TEK and MOBKL2B, in one patient. Although an apparently identical deletion was carried by the clinically normal father, we assumed that the patient's phenotype might be due to a recessive mutation in the other allele. However, sequence analysis of exons and splice junctions of these genes did not detect pathogenic or predisposing variants in the three patients. We suggest that the constellation of clinical signs in these patients constitutes a previously undescribed syndrome, whose genetic cause has yet to be identified.
authors.affiliation: Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Lucci-Cordisco
authors.forename: Salvatore
authors.initials: S
authors.lastname: Scommegna
authors.forename: Daniela
authors.initials: D
authors.lastname: Orteschi
authors.forename: Daniela
authors.initials: D
authors.lastname: Galeazzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Neri
authors.forename: Brunetto
authors.initials: B
authors.lastname: Boscherini
mesh_terms: D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9; D019066:Facies; D006801:Humans; D007018:Hypopituitarism / Q000151:congenital* / Q000175:diagnosis* / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D010641:Phenotype; D010902:Pituitary Gland / Q000378:metabolism / Q000473:pathology; D010907:Pituitary Hormones / Q000097:blood; D013577:Syndrome
chemical_list: D010907:Pituitary Hormones