Syndromic craniosynostosis due to complex chromosome 5 rearrangement andMSX2gene triplication

Abstract

Craniosynostosis is a common birth defect ( approximately 1/3,000 births) resulting from chromosome imbalances, gene mutations or unknown causes. We report a 6-month-old female with multiple sutural synostosis and prenatal onset growth deficiency, developmental delay, facial dysmorphism, congenital heart defect, and inguinal hernia. An integrated approach of standard cytogenetics, mBAND, locus-specific FISH, and 75 kb resolution array-CGH disclosed a complex chromosome 5 rearrangement, resulting in 3 paracentric inversions, 2 between-arm insertions, and partial duplication of 5q35. An extra copy of the MSX2 gene, which maps within the duplicated segment and is mutated in Boston-type craniosynostosis, was confirmed by molecular cytogenetic studies. Our study confirms that early fusion of cranial sutures commonly observed in the dup(5q) syndrome is caused by triplication of the MSX2 gene and strongly supports the crucial role of this gene in the development of craniofacial structures.

High-resolution SNP arrays in mental retardation diagnostics: how much do we gain?

“…Probes were prepared and FISH was performed as previously described. 26 An Eclipse 80i fluorescence microscope equipped with a computerized system (Genikon; Nikon, Florence, Italy) was used to analyze and acquire images. To confirm an imbalance, about 30 metaphase spreads and/or nuclei for each sample were counted.…”

Duplicación 5q34q35.3 que involucra el gen NSD1: región delimitada por microarreglos de hibridación genómica comparativa. A propósito de un caso

“…15 Por lo tanto, el defecto cardiaco observado en estos pacientes pudiera explicarse por la sobreexpresión de NKX2-5.…”

Duplication 5q and Deletion 9p due to a t(5;9)(q34;p23) in 2 Cousins with Features of Hunter-McAlpine Syndrome and Hypothyroidism

“…The present observation further confirms the etiology of the HMS phenotype from gain of the 5q35]qter region, expands the clinical pictures of partial trisomy 5q and monosomy 9p, and provides a comprehensive list of 160 patients with 5q distal duplication. Copyright © 2010 S. Karger AG, Basel Constitutional duplications for the 5q3 region have been documented in 158 patients including 1 90 subjects with a partial or complete 5q34 ] q35 duplication [Chen et al, 2006;Koolen et al, 2006;Bernardini et al, 2007;Wang et al, 2007;Kariminejad et al, 2009;Rivera and Vásquez-Velásquez, 2010; see supplementary material for overview, www.karger.com/doi/10.1159/000321647]. Aside from unspecific features (short stature, mild mental retardation, delayed puberty, chronic eczema, receding forehead, hernias, and reduced lifespan), 5q34 ] q35 duplications cause some distinct anomalies related to increased dosage of specific loci.…”

“…Vásquez-Velásquez et al Cytogenet Genome Res 2011;132:233-238 234 2006], and heart defects to the NKX2-5 gene at 5q35.1 [Chen et al, 2006;Bernardini et al, 2007].…”

“…Aside from unspecific features (short stature, mild mental retardation, delayed puberty, chronic eczema, receding forehead, hernias, and reduced lifespan), 5q34 ] q35 duplications cause some distinct anomalies related to increased dosage of specific loci. Thus, holoprosencephaly and preaxial polydactyly have been ascribed to the FBXW11 gene at 5q35.1 [Koolen et al, 2006], craniosynostosis and secondary microcephaly to the MSX2 gene at 5q35.2 [Shiihara et al, 2004;Bernardini et al, 2007;Wang et al, 2007;Kariminejad et al, 2009], microcephaly and short stature to the NSD1 gene at 5q35.2 [Chen et al, …”