Marfan syndrome: Report of a complex phenotype due to a 15q21.1 contiguos gene deletion encompassing FBN1, and literature review.
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder that primarily involves skeletal, ocular, and cardiovascular systems with large inter- and intra-familial variability in terms of age of onset, severity, and aortic disease. The causal gene, FBN1, encodes for fibrillin 1, a multi-domain glycoprotein essential for many biological functions, including deposition and formation of elastic fibers. Reports describing chromosomal alterations involving FBN1 are rare, but in the last years their number has increased after copy number state analyses, such as multiplex ligation-dependent probe amplification and microarray-based comparative genomic hybridization, were adopted as routine diagnostic tools. Herein we report a patient with MFS and an atypical facial appearance and neuropsychiatric involvement likely not attributable to MFS due to a 15q21.1 deletion that involves part of FBN1 and 13 additional contiguous genes listed in OMIM. We compare his phenotype with those of the few patients described in the literature who share similar 15q11.2 deletions. This report expands the phenotype of patients with 15q11.2 deletion involving FBN1 and its contiguous genes, and suggests a possible role for these other genes in the pathogenesis of the observed unusual clinical signs that are not explained by FBN1 haploinsufficiency. © 2016 Wiley Periodicals, Inc.
Division of Biology and Genetics, Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, Brescia, Italy.
Chiara
C
Dordoni
Division of Biology and Genetics, Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, Brescia, Italy.
Claudia
C
Ciaccio
Division of Biology and Genetics, Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, Brescia, Italy.
Graziano
G
Santoro
Division of Dermatology, Department of Clinical and Experimental Sciences, Spedali Civili University Hospital, Brescia, Italy.
Marina
M
Venturini
Azienda Istituti Ospitalieri, Medical Genetics, Cremona, Italy.
Ugo
U
Cavallari
Division of Biology and Genetics, Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, Brescia, Italy.
Marco
M
Ritelli
Division of Biology and Genetics, Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, Brescia, Italy.
Marina
M
Colombi
D000293:Adolescent; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15; D055028:Comparative Genomic Hybridization; D019066:Facies; D000071838:Fibrillin-1 / Q000235:genetics*; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype
D000071838:Fibrillin-1
15q21.1 microdeletion; FBN1; MLPA; Marfan syndrome; aCGH; gross rearrangement