RT Journal Article
SR Electronic
T1 3q27.3 microdeletional syndrome: a recognisable clinical entity associating dysmorphic features, marfanoid habitus, intellectual disability and psychosis with mood disorder
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 21
OP 27
DO 10.1136/jmedgenet-2013-101939
VO 51
IS 1
A1 Julien Thevenon
A1 Patrick Callier
A1 Hélène Poquet
A1 Iben Bache
A1 Bjorn Menten
A1 Valérie Malan
A1 Maria Luigia Cavaliere
A1 Jean-Paul Girod
A1 Christel Thauvin-Robinet
A1 Salima El Chehadeh
A1 Jean-Michel Pinoit
A1 Frederic Huet
A1 Bruno Verges
A1 Jean-Michel Petit
A1 Anne-Laure Mosca-Boidron
A1 Nathalie Marle
A1 Francine Mugneret
A1 Alice Masurel-Paulet
A1 Antonio Novelli
A1 Zeynep Tümer
A1 Bart Loeys
A1 Stanislas Lyonnet
A1 Laurence Faivre
YR 2014
UL http://jmg.bmj.com/content/51/1/21.abstract
AB Background Since the advent of array-CGH, numerous new microdeletional syndromes have been delineated while others remain to be described. Although 3q29 subtelomeric deletion is a well-described syndrome, there is no report on 3q interstitial deletions. Methods We report for the first time seven patients with interstitial deletions at the 3q27.3q28 locus gathered through the Decipher database, and suggest this locus as a new microdeletional syndrome. Results The patients shared a recognisable facial dysmorphism and marfanoid habitus, associated with psychosis and mild to severe intellectual disability (ID). Most of the patients had no delay in gross psychomotor acquisition, but had severe impaired communicative and adaptive skills. Two small regions of overlap were defined. The first one, located on the 3q27.3 locus and common to all patients, was associated with psychotic troubles and mood disorders as well as recognisable facial dysmorphism. This region comprised several candidate genes including SST, considered a candidate for the neuropsychiatric findings because of its implication in interneuronal migration and differentiation processes. A familial case with a smaller deletion allowed us to define a second region of overlap at the 3q27.3q28 locus for marfanoid habitus and severe ID. Indeed, the common morphological findings in the first four patients included skeletal features from the marfanoid spectrum: scoliosis (4/4), long and thin habitus with leanness (average Body Mass Index of 15 (18.5<N<25)) (4/4), arachnodactyly (3/4) and pectus excavatum (2/4)). This phenotype could be explained by the deletion of the AHSG gene, which encodes a secreted protein implicated in bone maturation and the TGFb signalling pathway. Conclusions We report on a new microdeletional syndrome that associates with a recognisable facial dysmorphism and marfanoid habitus including scoliosis, neuropsychiatric disorders of the psychotic spectrum and moderate to severe ID.