Subtelomere FISH analysis of 11 688 cases: an evaluation of the frequency and pattern of subtelomere rearrangements in individuals with developmental disabilities

Ravnan, J. Britt; Tepperberg, James; Papenhausen, Peter; Lamb, Allen N.; Hedrick, Julie; Eash, D; Ledbetter, David H.; Martin, Christa Lese

doi:10.1136/jmg.2005.036350

Cited by 355 publications

(363 citation statements)

References 18 publications

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“…In accordance with the report by Ravnan et al 18 showing that the majority of chromosomal terminal deletions were de novo (48/60 familial studies), we confirmed in our series that, strictly speaking, no patient had inherited the 2q37 deletion from his/her parents. The 2q polymorphism is a common condition in the population (5%).…”

Section: Parental Analysissupporting

confidence: 93%

“…In the largest study of the kind, in which the telomeres of 11 688 individuals were investigated, the 2qtel subtelomeric deletion was a frequently encountered variation, observed in seven patients as a pure deletion. 18 In the study by Ravnan et al, near half of the phenotypically altered patients had terminal 2q deletions, but it was not explicitly indicated whether the 2q deletion was a deleterious del 2q37 or only the common polymorphism. Indeed, the first subtelomeric FISH probes used encompassed the polymorphic loci.…”

Section: Mappingmentioning

confidence: 99%

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The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients

et al. 2012

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Section: Parental Analysissupporting

confidence: 93%

Section: Mappingmentioning

confidence: 99%

The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients

et al. 2012

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“…For the last three patients with 2pter deletion reported in the literature, clinical information was unavailable. 3,5 Clinical features of the patients reported in the literature are listed in Table 2.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8] Becker et al 6 reported a patient with a de novo pure 2p25.2 deletion, bilateral severe talipes equinovarus, pulmonary valve stenosis, nasal polyps, mild psychomotor retardation, and overweightness with food seeking behaviour. Several patients were then reported presenting with obesity, intellectual disability (ID), and 2p25 deletion.…”

Section: Introductionmentioning

confidence: 99%

Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes

et al. 2013

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Obesity is a common but highly, clinically, and genetically heterogeneous disease. Deletion of the terminal region of the short arm of chromosome 2 is rare and has been reported in about 13 patients in the literature often associated with a Prader-Willi-like phenotype. We report on five unrelated patients with 2p25 deletion of paternal origin presenting with earlyonset obesity, hyperphagia, intellectual deficiency, and behavioural difficulties. Among these patients, three had de novo pure 2pter deletions, one presented with a paternal derivative der(2)t(2;15)(p25.3;q26) with deletion in the 2pter region and the last patient presented with an interstitial 2p25 deletion. The size of the deletions was characterized by SNP array or array-CGH and was confirmed by fluorescence in situ hybridization (FISH) studies. Four patients shared a 2p25.3 deletion with a minimal critical region estimated at 1.97 Mb and encompassing seven genes, namely SH3HYL1, ACP1, TMEMI8, SNTG2, TPO, PXDN, and MYT1L genes. The fifth patient had a smaller interstitial deletion encompassing the TPO, PXDN, and MYT1L genes. Paternal origin of the deletion was determined by genotyping using microsatellite markers. Analysis of the genes encompassed in the deleted region led us to speculate that the ACP1, TMEM18, and/or MYT1L genes might be involved in early-onset obesity. In addition, intellectual deficiency and behavioural troubles can be explained by the heterozygous loss of the SNTG2 and MYT1L genes. Finally, we discuss the parent-of-origin of the deletion.

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“…1,5,8 The identification of patients with atypical 4p deletions has provided key insight into which regions of 4p16.3 may (or may not) contribute to the pathogenesis of WHS. For example, small terminal deletions (up to 400 kb) have been inherited from phenotypically normal individuals; [12][13][14] indicating that monosomy of this region is likely benign. 11 Between B1.8 and 2.0 Mb from the 4p terminus, two adjacent critical regions were proposed based on the smallest region of overlap (SRO) among the deletions of individuals with or without the core features of WHS.…”

Section: Introductionmentioning

confidence: 99%

Deletions involving genes WHSC1 and LETM1 may be necessary, but are not sufficient to cause Wolf–Hirschhorn Syndrome

et al. 2013

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Wolf-Hirschhorn syndrome (WHS) is a complex genetic disorder caused by the loss of genomic material from the short arm of chromosome 4. Genotype-phenotype correlation studies indicated that the loss of genes within 4p16.3 is necessary for expression of the core features of the phenotype. Within this region, haploinsufficiency of the genes WHSC1 and LETM1 is thought to be a major contributor to the pathogenesis of WHS. We present clinical findings for three patients with relatively small (o400 kb) de novo interstitial deletions that overlap WHSC1 and LETM1. 3D facial analysis was performed for two of these patients. Based on our findings, we propose that hemizygosity of WHSC1 and LETM1 is associated with a clinical phenotype characterized by growth deficiency, feeding difficulties, and motor and speech delays. The deletion of additional genes nearby WHSC1 and LETM1 does not result in a marked increase in the severity of clinical features, arguing against their haploinsufficiency. The absence of seizures and typical WHS craniofacial findings in our cohort suggest that deletion of distinct or additional 4p16.3 genes is necessary for expression of these features. Altogether, these results show that although loss-offunction for WHSC1 and/or LETM1 contributes to some of the features of WHS, deletion of additional genes is required for the full expression of the phenotype, providing further support that WHS is a contiguous gene deletion disorder.

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Subtelomere FISH analysis of 11 688 cases: an evaluation of the frequency and pattern of subtelomere rearrangements in individuals with developmental disabilities

Abstract: This study of subtelomere rearrangements is a 20 fold increase in number over the previously reported largest study and represents an unbiased analysis of subtelomere rearrangements in a large, unselected patient population.

Cited by 355 publications

References 18 publications

The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients

The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients

Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes

Deletions involving genes WHSC1 and LETM1 may be necessary, but are not sufficient to cause Wolf–Hirschhorn Syndrome

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