Partial monosomy of distal 10q: Three new cases and a review

Waggoner, Darrel; Chow, Clara K.; Dowton, S. Bruce; Watson, Michael S.

doi:10.1002/(sici)1096-8628(19990903)86:1<1::aid-ajmg1>3.3.co;2-1

Cited by 19 publications

(29 citation statements)

References 17 publications

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“…The typical features associated with these deletions include a prominent, beaked nose, malformed ears, mental retardation, cardiac defects, and anogenital malformations. 25 The features of the patient reported here do not overlap with this reported phenotype, giving more credence to the likelihood that his deletion is not related to his phenotype.…”

Section: Discussionsupporting

confidence: 53%

"Molecular rulers" for calibrating phenotypic effects of telomere imbalance

Martin

Waggoner

Wong

et al. 2002

Journal of Medical Genetics

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As a result of the increasing use of genome wide telomere screening, it has become evident that a significant proportion of people with idiopathic mental retardation have subtle abnormalities involving the telomeres of human chromosomes. However, during the course of these studies, there have also been telomeric imbalances identified in normal people that are not associated with any apparent phenotype. We have begun to scrutinise cases from both of these groups by determining the extent of the duplication or deletion associated with the imbalance. Five cases were examined where the telomere rearrangement resulted in trisomy for the 16p telomere. The size of the trisomic segment ranged from ∼4-7 Mb and the phenotype included mental and growth retardation, brain malformations, heart defects, cleft palate, pancreatic insufficiency, genitourinary abnormalities, and dysmorphic features. Three cases with telomeric deletions without apparent phenotypic effects were also examined, one from 10q and two from 17p. All three deletions were inherited from a phenotypically normal parent carrying the same deletion, thus without apparent phenotypic effect. The largest deletion among these cases was ∼600 kb on 17p. Similar studies are necessary for all telomeric regions to differentiate between those telomeric rearrangements that are pathogenic and those that are benign variants. Towards this goal, we are developing "molecular rulers" that incorporate multiple clones at each telomere that span the most distal 5 Mb region. While telomere screening has enabled the identification of telomere rearrangements, the use of molecular rulers will allow better phenotype prediction and prognosis related to these findings. U nbalanced submicroscopic telomere rearrangements are a significant cause of idiopathic mental retardation with or without congenital malformations, accounting for approximately 5% of these cases. [1][2][3][4][5][6][7] With the development of a second generation set of telomere specific clones, 8 telomere screening is now readily available in many laboratories and is being used extensively in the evaluation of children with mental retardation and congenital anomalies. The results of these investigations are not only providing explanations for previously unexplained cases of mental retardation, but are also further defining the frequency of telomeric rearrangements in various clinical populations and clarifying the phenotype associated with these rearrangements. Furthermore, during the course of these studies, telomeric imbalances have also been identified in normal subjects without any apparent phenotype.3 5 6 9 These observations suggest that not all telomere imbalances result in a phenotype and that the lack of phenotypic effect may be related to the size of the rearrangement or the involvement of regions of the genome that are tolerant to dosage imbalances.Despite these advances, there is a paucity of information regarding the genotype/phenotype correlations of many of the telomere imbalances discovered, complicating t...

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Section: Discussionsupporting

confidence: 53%

"Molecular rulers" for calibrating phenotypic effects of telomere imbalance

Martin

Waggoner

Wong

et al. 2002

Journal of Medical Genetics

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“…23 One was a 6 year old, moderately delayed female with an additional trisomy of 16qter owing to a familial t(5;16) and mild dysmorphic features (dense hair, prominent forehead, large mouth, thin upper lip, and thick lower lip) and normal growth. The same group reported another unrelated 12 year old female with a similar deletion 5qter and duplication 16qter, but this time de novo, and a lownormal IQ (80)(81)(82)(83)(84)(85)(86)(87)(88)(89), normal growth, mild facial dysmorphism (mild epicanthic folds, upward slanting palpebral fissures, low nasal bridge, short philtrum), slender hands and feet, cardiac abnormalities (mild pulmonary valve stenosis and large VSD), and vesicoureteric reflux.…”

Section: Qmentioning

confidence: 99%

Telomeres: a diagnosis at the end of the chromosomes

Vries

Winter

Schinzel³

et al. 2003

Journal of Medical Genetics

215

190

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“…The vast majority of studies have reported terminal deletions, with breakpoints ranging from 10q23.3 to 10q26.3 as determined by conventional cytogenetic techniques, and only a few cases of 10q interstitial deletions have been previously identified (1)(2)(3)(4)(5). The vast majority of studies have reported terminal deletions, with breakpoints ranging from 10q23.3 to 10q26.3 as determined by conventional cytogenetic techniques, and only a few cases of 10q interstitial deletions have been previously identified (1)(2)(3)(4)(5).…”

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confidence: 99%

Identification of critical regions for clinical features of distal 10q deletion syndrome

et al. 2009

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Array comparative genomic hybridization studies were performed to further characterize cytogenetic abnormalities found originally by karyotype and fluorescence in situ hybridization in five clinical cases of distal 10q deletions, including several with complex cytogenetic rearrangements and one with a partial male-to-female sex-reversal phenotype. These results have enabled us to narrow the previously proposed critical regions for the craniofacial, urogenital, and neuropsychiatric disease-related manifestations associated with distal 10q deletion syndrome. Furthermore, we propose that haploinsufficiency of the DOCK1 gene may play a crucial role in the pathogenesis of the 10q deletion syndrome. We hypothesize that alteration of DOCK1 and/or other genes involved in regulation and signaling of multiple pathways can explain the wide range of phenotypic variability between patients with similar or identical cytogenetic abnormalities.

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Partial monosomy of distal 10q: Three new cases and a review

Cited by 19 publications

References 17 publications

"Molecular rulers" for calibrating phenotypic effects of telomere imbalance

"Molecular rulers" for calibrating phenotypic effects of telomere imbalance

Telomeres: a diagnosis at the end of the chromosomes

Identification of critical regions for clinical features of distal 10q deletion syndrome

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