Deletion of REXO1L1 locus in a patient with malabsorption syndrome, growth retardation, and dysmorphic features: a novel recognizable microdeletion syndrome?
BACKGROUND
Copy number variations (CNVs) can contribute to genetic variation among individuals and/or have a significant influence in causing diseases. Many studies consider new CNVs' effects on protein family evolution giving rise to gene duplicates or losses. "Unsuccessful" duplicates that remain in the genome as pseudogenes often exhibit functional roles. So, changes in gene and pseudogene number may contribute to development or act as susceptibility alleles of diseases.


METHODS
We report a de novo heterozygous 271 Kb microdeletion at 8q21.2 region which includes the family of REXO1L genes and pseudogenes in a young man affected by global development delay, progeroid signs, and gastrointestinal anomalies. Molecular and cellular analysis showed that the REXO1L1 gene hemizygosity in a patient's fibroblasts induces genetic instability and increased apoptosis after treatment with different DNA damage-induced agents.


CONCLUSIONS
The present results support the hypothesis that low copy gene number within REXO1L1 cluster could play a significant role in this complex clinical and cellular phenotype.
Fondazione Policlinico Tor Vergata, Rome, Italy. d.apice@med.uniroma2.it.
Maria Rosaria
MR
D'Apice
Mendel Institute, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. a.novelli@css-mendel.it.
Antonio
A
Novelli
Department of Biology, "Roma Tre" University, Rome, Italy. dimasi@uniroma3.it.
Alessandra
A
di Masi
Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy. michela.biancolella@uniroma2.it.
Michela
M
Biancolella
Department of Biology, "Roma Tre" University, Rome, Italy. antoccia@uniroma3.it.
Antonio
A
Antoccia
Department of Biology, "Roma Tre" University, Rome, Italy. francescagullotta@hotmail.com.|Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy. francescagullotta@hotmail.com.
Francesca
F
Gullotta
Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy. normalicata@hotmail.com.|Department of Neuroscience, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy. normalicata@hotmail.com.
Norma
N
Licata
Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy. danymin@gmail.com.
Daniela
D
Minella
Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy. testabarbara@libero.it.
Barbara
B
Testa
Fondazione Policlinico Tor Vergata, Rome, Italy. annamaria.nardone@ptvonline.it.
Anna Maria
AM
Nardone
Pathological Anatomy Unit, University Tor Vergata, Rome, Italy. giampiero.palmieri@uniroma2.it.
Giampiero
G
Palmieri
Department of Internal Medicine, Gastrointestinal Unit, Tor Vergata University of Rome, Rome, Italy. clbmme00@uniroma2.it.
Emma
E
Calabrese
Department of Internal Medicine, Gastrointestinal Unit, Tor Vergata University of Rome, Rome, Italy. biancone@med.uniroma2.it.
Livia
L
Biancone
Department of Biology, "Roma Tre" University, Rome, Italy. tanzarel@uniroma3.it.
Caterina
C
Tanzarella
Institute of Translational Pharmacology, CNR, Rome, Italy. marina.frontali@ift.cnr.it.
Marina
M
Frontali
Fondazione Policlinico Tor Vergata, Rome, Italy. sangiuolo@med.uniroma2.it.|Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy. sangiuolo@med.uniroma2.it.
Federica
F
Sangiuolo
Fondazione Policlinico Tor Vergata, Rome, Italy. novelli@med.uniroma2.it.|Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy. novelli@med.uniroma2.it.|San Pietro Fatebenefratelli Hospital, Rome, Italy. novelli@med.uniroma2.it.
Giuseppe
G
Novelli
Department of Internal Medicine, Gastrointestinal Unit, Tor Vergata University of Rome, Rome, Italy. pallone@med.uniroma2.it.
Francesco
F
Pallone
D000293:Adolescent; D001072:Apraxias / Q000150:complications; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000150:complications*; D005786:Gene Expression Regulation / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D008286:Malabsorption Syndromes / Q000150:complications* / Q000235:genetics*; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D010641:Phenotype; D011544:Pseudogenes / Q000235:genetics; D017384:Sequence Deletion; D055815:Young Adult