Evidence for a new microdeletion syndrome in 15q21

Liehr, Thomas; Starke, Heike; Heller, Ana Helena; Weise, Alexander; Beensen, Volkmar; Senger, Gabriele; Kittner, G; Prechtel, M; Claussen, Uwe; Seidel, Joerg

doi:10.3892/ijmm.11.5.575

Cited by 13 publications

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“…However, in most of these reports, the deletion of FBN1 or the presence of marfanoid features are not discussed [24][25][26][27][28][29] . In four reports, the deletion of FBN1 is confirmed by molecular techniques, with marfanoid features in three cases 18,19,21 and absence of marfanoid features in one case, which could be due to the young age of this patient.…”

Section: Discussionmentioning

confidence: 99%

The clinical spectrum of complete FBN1 allele deletions

et al. 2010

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The most common mutations found in FBN1 are missense mutations (56%), mainly substituting or creating a cysteine in a cbEGF domain. Other mutations are frameshift, splice and nonsense mutations. There are only a few reports of patients with marfanoid features and a molecularly proven complete deletion of a FBN1 allele. We describe the clinical features of 10 patients with a complete FBN1 gene deletion. Seven patients fulfilled the Ghent criteria for Marfan syndrome (MFS). The other three patients were examined at a young age and did not (yet) present the full clinical picture of MFS yet. Ectopia lentis was present in at least two patients. Aortic root dilatation was present in 6 of the 10 patients. In three patients, the aortic root diameter was on the 95th percentile and in one patient, the diameter of the aortic root was normal, the cross-section, however, had a cloverleaf appearance. Two patients underwent aortic root surgery at a relatively young age (27 and 34 years). Mitral valve prolapse was present in 4 of the 10 patients, and billowing of the mitral valve in 1. All patients had facial and skeletal features of MFS. Two patients with a large deletion extending beyond the FBN1 gene had an extended phenotype. We conclude that complete loss of one FBN1 allele does not predict a mild phenotype, and these findings support the hypothesis that true haploinsufficiency can lead to the classical phenotype of Marfan syndrome.

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Section: Discussionmentioning

confidence: 99%

The clinical spectrum of complete FBN1 allele deletions

et al. 2010

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“…28 -30 A more recent report also supports the presence of a microdeletion-syndrome involving obesity at 15q21, which possibly overlaps with our breakpoint region on chromosome 15. 31 The chromosome 4 breakpoint is located 133 kb 5 0 unc-5 homologue C (Caenorhabditis elegans; UNC5C). This juxtaposition of the RORa1 5 0 to the UNC5C results in the expression of a novel fusion transcript in frame, which includes exon 1 of the RORa1 gene and the UNC5C gene from exon 2.…”

Section: Discussionmentioning

confidence: 99%

RAR-related orphan receptor A isoform 1 (RORa1) is disrupted by a balanced translocation t(4;15)(q22.3;q21.3) associated with severe obesity

et al. 2005

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We have identified a family comprising a mother and two children with idiopathic and profound obesity body mass index (BMI) 41 -49 kg/m 2 . The three family members carry a balanced reciprocal chromosome translocation t(4;15). We present here the clinical features of the affected individuals as well as the physical mapping and cloning of the chromosomal breakpoints. A detailed characterisation of the chromosomal breakpoints at chromosomes 4 and 15 revealed that the translocation is almost perfectly balanced with a very short insertion/deletion. The chromosome 15 breakpoint is positioned in intron 1 of the RAR-related orphan receptor A isoform 1 (RORa1) and the chromosome 4 breakpoint is positioned 133 kb telomeric to the transcriptional start of the unc-5 homolog B (UNC5C) and 154 kb centromeric of the transcriptional start of the pyruvate dehydrogenase (lipoamide) alpha 2 (PDHA2). The rearrangement creates a fusion gene, which includes the RORa1 exon 1 and UNC5C that is expressed in frame in adipocytes from the affected patients. We also show that this transcript is translated into a protein. From previous reports, it is shown that RORa1 is implicated in the regulation of adipogenesis and lipoprotein metabolism. We hypothesise that the obesity in this family is caused by (i) haploinsufficiency for RORa1 or, (ii) a gain of function mechanism mediated by the RORa1 -UNC5C fusion gene.

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“…b Martin et al [1990]; Lalani et al [2006]; Tempesta et al [2008]; Yamamoto et al [2014]. severe ID, growth retardation, and facial dysmorphisms, such as a beak-like nose with hypoplastic alae nasi and a thin upper lip among others [Fryns et al, 1982;Yip et al, 1987;Formiga et al, 1988;Fukushima et al, 1990;Martin et al, 1990;Koivisto et al, 1999;Liehr et al, 2003;Shur et al, 2003;Pramparo et al, 2005;Lalani et al, 2006;Tempesta et al, 2008]. Here, we report on a patient who displayed a complex phenotype.…”

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confidence: 97%

“…different segmental losses involving 15q21q22 have been reported [Fryns et al, 1982;Yip et al, 1987;Formiga et al, 1988;Fukushima et al, 1990;Martin et al, 1990;Koivisto et al, 1999;Liehr et al, 2003;Shur et al, 2003;Pramparo et al, 2005;Lalani et al, 2006;Tempesta et al, 2008;Yamamoto et al, 2014], and only 5 of them have been characterized by comparative genomic hybridization (aCGH) [Liehr et al, 2003;Shur et al, 2003;Pramparo et al, 2005;Lalani et al, 2006;Tempesta et al, 2008] Fryns et al [1982]; Yip et al [1987]; Liehr et al [2003]; Pramparo et al [2005]. b Martin et al [1990]; Lalani et al [2006]; Tempesta et al [2008]; Yamamoto et al [2014].…”

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confidence: 99%

“…In recent years, an increasing number of cases have been recognized as a result of recurrent DNA rearrangements involving unstable genomic regions. Array technology has allowed the identification of associations of several new regions with new syndromes, including the 15q21 region that is related to a very rare chromosomal anomaly [Liehr et al, 2003;Shur et al, 2003;Pramparo et al, 2005; Lalani et al, 2006; Stankiewic and Beaudet, 2007;Tempesta et al, 2008;Sagoo et al, 2009]. To date, only 14 patients with Key Words 15q21q22 deletion · Affymetrix CytoScan HD Array · Chromosomal rearrangement · GTG banding · Intellectual disability…”

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confidence: 99%

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Clinical and Molecular Characterization of a Patient with 15q21.2q22.2 Deletion Syndrome

Velázquez-Wong

Esparza‐Garrido

Velázquez-Flores

et al. 2014

Cytogenet Genome Res

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We report on a 16-year-old girl with a complex phenotype, including intellectual disability, facial dysmorphisms, and obesity. During her infancy, she presented with weak sucking, global developmental delay, and later with excessive eating with central obesity. The girl was clinically diagnosed with probable Prader-Willi syndrome. Chromosomal analysis showed a de novo deletion 46,XX,del(15)(q21q22). However, the use of the Affymetrix CytoScan HD Array defined the exact breakpoints of the deleted 15q21q22 region. The imbalance, about 10.5 Mb in size, is to date the second largest deletion ever described in this chromosomal region. In addition, our patient carries a microdeletion in the 1q44 region and a gain in 9p24. The array result was arr[hg19] 9p24.1(6,619,823-6,749,335)×3, 1q44(248,688,586-248,795,277)×1, 15q21.2 q22.2(50,848,301-61,298,006)×1. Although our patient presents additional chromosomal alterations, we provide a correlation between the clinical findings and the phenotype of the 15q21 deletion syndrome.

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Evidence for a new microdeletion syndrome in 15q21

Cited by 13 publications

References 0 publications

The clinical spectrum of complete FBN1 allele deletions

The clinical spectrum of complete FBN1 allele deletions

RAR-related orphan receptor A isoform 1 (RORa1) is disrupted by a balanced translocation t(4;15)(q22.3;q21.3) associated with severe obesity

Clinical and Molecular Characterization of a Patient with 15q21.2q22.2 Deletion Syndrome

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