Premium
Three unrelated patients with congenital anterior pituitary aplasia and a characteristic physical and neuropsychological phenotype: A new syndrome?
Author(s) -
LucciCordisco Emanuela,
Scommegna Salvatore,
Orteschi Daniela,
Galeazzi Daniela,
Neri Giovanni,
Boscherini Brunetto
Publication year - 2012
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35579
Subject(s) - aplasia , phenotype , neuropsychology , medicine , pediatrics , biology , psychiatry , genetics , cognition , gene
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. © 2012 Wiley Periodicals, Inc.