title: Delineation of a recognizable phenotype for the recurrent LCR22-C to D/E atypical 22q11.2 deletion.
abstract: The 22q11.2 deletion syndrome is typically caused by haploinsufficiency of a 3 Mb region that extends from LCR22-A until LCR22-D, while the recurrent recombination between any of the LCR22-D to H causes the 22q11.2 distal deletion syndrome. Here, we describe three patients with a de novo atypical ∼1.4 Mb 22q11.2 deletion that involves LCR22-C to a region beyond D (LCR22-C to D/E), encompassing the distal portion of the typical deleted region and the proximal portion of the distal deletion. We also review six previous published patients with the same rearrangement and compare their features with those found in patients with overlapping deletions. Patients with LCR22-C to D/E deletion present a recognizable phenotype characterized by facial dysmorphic features, high frequency of cardiac defects, including conotruncal defects, prematurity, growth restriction, microcephaly, and mild developmental delay. Genotype-phenotype analysis of the patients indicates that CRKL and MAPK1 genes play an important role as causative factors for the main clinical features of the syndrome. In particular, CRKL gene seems to be involved in the occurrence of conotruncal cardiac anomalies, mainly tetralogy of Fallot. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Medical Genetics, Complejo Hospitalario de Navarra, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Amaya
authors.initials: A
authors.lastname: Bengoa-Alonso
authors.affiliation: Department of Medical Genetics, Complejo Hospitalario de Navarra, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Artigas-López
authors.affiliation: Department of Medical Genetics, Complejo Hospitalario de Navarra, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Moreno-Igoa
authors.affiliation: Department of Medical Genetics, Complejo Hospitalario de Navarra, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cattalli
authors.affiliation: Department of Medical Genetics, Complejo Hospitalario de Navarra, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Hernández-Charro
authors.affiliation: Department of Medical Genetics, Complejo Hospitalario de Navarra, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Ramos-Arroyo
mesh_terms: D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D004062:DiGeorge Syndrome / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D056726:Genetic Association Studies; D057238:Growth Charts; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010641:Phenotype; D056916:Segmental Duplications, Genomic
keywords: 22q11 deletion; CRKL; MAPK1; congenital heart defect; growth retardation; microcephaly; prematurity