Dissection of partial 21q monosomy in different phenotypes: clinical and molecular characterization of five cases and review of the literature.
BACKGROUND
Partial deletion of chromosome 21q is a very rare chromosomal abnormality associated with highly variable phenotypes, such as facial dysmorphic features, heart defects, seizures, psychomotor delay, and severe to mild intellectual disability, depending on the location and size of deletions. So far, three broad deletion regions of 21q have been correlated with the clinical phenotype.


RESULTS
We described the clinical and genetic features of three family members (father and two siblings) and other two unrelated patients with very wide range in age of diagnosis. All of them showed intellectual disability with very variable symptoms, from mild to severe, and carried 21q interstitial deletions with different sizes and position, as detected by conventional karyotype and array-CGH.


CONCLUSIONS
Our study provided additional cases of partial 21q deletions, allowing to better delineate the genotype-phenotype correlations. In contrast to previous observations, we showed that deletions of the 21q proximal region are not necessarily associated with severe phenotypes and, therefore, that mild phenotypes are not exclusively related to distal deletions. To the best of our knowledge, this is the first report showing 21q deletions in adult patients associated with mild phenotypes, mainly consisting of neurobehavioral abnormalities, such as obsessive-compulsive disorders, poor social interactions and vulnerability to psychosis.
Department of Molecular Medicine, University of Pavia, Via Forlanini 14, 27100 Pavia, Italy.
Edoardo
E
Errichiello
Department of Molecular Medicine, University of Pavia, Via Forlanini 14, 27100 Pavia, Italy.
Francesca
F
Novara
National Neurological Institute IRCCS C, Mondino, Pavia, Italy.
Anna
A
Cremante
National Neurological Institute IRCCS C, Mondino, Pavia, Italy.
Annapia
A
Verri
Mother-Child Department, Child Neurology and Psychiatry Unit, Spedali Civili, Brescia, Italy.
Jessica
J
Galli
Mother-Child Department, Child Neurology and Psychiatry Unit, Spedali Civili, Brescia, Italy.
Elisa
E
Fazzi
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Daniela
D
Bellotti
Department of Pediatrics, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
Laura
L
Losa
Department of Pediatrics, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
Mariangela
M
Cisternino
Department of Molecular Medicine, University of Pavia, Via Forlanini 14, 27100 Pavia, Italy.
Orsetta
O
Zuffardi
Array Comparative Genomic Hybridization (array-CGH); BTG3 (BTG family; Behavioral disorders; DNA Copy Number Variations (CNVs); GRIK1 (glutamate receptor; Intellectual Disability (ID); Ionotropic; Kainate 1); Member 3); Partial 21q monosomy; RBM11 (RNA binding motif protein 11)