Transmitted cytogenetic abnormalities in patients with mental retardation: Pathogenic or normal variants?

Bisgaard, Anne‐Marie; Kirchhoff, Maria; Brandt, Carsten A.; Hove, Hanne; Jepsen, Birgit; Jensen, Tim; Ullmann, Reinhard; Skovby, Flemming

doi:10.1016/j.ejmg.2007.03.004

Cited by 41 publications

(42 citation statements)

References 38 publications

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“…5 She was born at 35 weeks gestation to non-consanguineous Caucasian Danish parents with a birth weight of 1.82 kg (10th) and OFC 28.3 cm (0.4th centile). She had trigonocephaly with a fused metopic suture (requiring surgery at 9 months of age), prominent eyes, upslanting palpebral fissures, epicanthus, glabella nevus flammeus, high and narrow palate, hypertrichosis, low temporal hairline, synophrys, retrognathia, deep palmar creases, and sacral dimple.…”

Section: Clinical Datamentioning

confidence: 99%

“…Genetic study: array comparative genomic hybridization Array comparative genomic hybridization (CGH) was performed using standardized protocols with differing platforms used according to local arrangements (using the Bluegnome cytochip 1 Mb BAC array, tiling path 32K BAC array, 5 or the Agilent Wessex customized 44K oligoarray). All patients except patients 4 and 12 had array CGH performed.…”

Section: Biochemical Study: Analysis Of the Cholesterol Biosynthesis mentioning

confidence: 99%

“…We propose diagnostic criteria for the clinical diagnosis of BOS, describe 10 previously unreported patients, and provide an update on four of those reported previously. [4][5][6] The characteristic features of this condition are typical facial appearance (trigonocephaly/prominent metopic ridge, retrognathia, prominent eyes with hypoplastic supraorbital ridges, upslanting palpebral fissures, depressed nasal bridge, anteverted nares, low-set and posteriorly rotated ears, palatal abnormalities and broad alveolar ridges, flammeus nevus, low anterior hairline), microcephaly, IUGR and short stature, joint abnormalities, abnormal tone, severe/profound developmental delay, susceptibility to infections, feeding difficulties, and high infant mortality. Owing to the overlap of many of the clinical features of BOS with some of the disorders of cholesterol biosynthesis, such as Smith-Lemli-Opitz syndrome, desmosterolosis, and lathosterolosis, we decided to analyze cholesterol biosynthesis precursors using tandem mass spectrometry.…”

Section: Introductionmentioning

confidence: 99%

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Bohring–Opitz (Oberklaid–Danks) syndrome: clinical study, review of the literature, and discussion of possible pathogenesis

et al. 2011

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Bohring-Opitz syndrome (BOS) is a rare congenital disorder of unknown etiology diagnosed on the basis of distinctive clinical features. We suggest diagnostic criteria for this condition, describe ten previously unreported patients, and update the natural history of four previously reported patients. This is the largest series reported to date, providing a unique opportunity to document the key clinical features and course through childhood. Investigations undertaken to try and elucidate the underlying pathogenesis of BOS using array comparative genomic hybridization and tandem mass spectrometry of cholesterol precursors did not show any pathogenic changes responsible.

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Section: Clinical Datamentioning

confidence: 99%

Section: Biochemical Study: Analysis Of the Cholesterol Biosynthesis mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bohring–Opitz (Oberklaid–Danks) syndrome: clinical study, review of the literature, and discussion of possible pathogenesis

et al. 2011

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“…The general rule that de novo chromosomal imbalances are more likely to be clinically significant, while familial CNVs are less likely does not always hold true and can never be the sole criterion for clinical interpretation. Several studies have shown the clinical relevance of inherited CNVs and therefore the de novo origin of a CNV is not by itself a good indicator of its clinical relevance [Bisgaard et al, 2007;De Ravel et al, 2006;Mencarelli et al, 2008].…”

Section: Introductionmentioning

confidence: 99%

The introduction of arrays in prenatal diagnosis: A special challenge

et al. 2012

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“…Several studies have shown the clinical relevance of inherited CNVs and therefore the de novo origin of a CNV is not a good indicator of its clinical relevance. [5][6][7] A more reliable way of determing the clinical relevance of a CNV is to compare it with CNVs gathered in large databases with data of healthy controls. The Database of Genomic Variants (http://projects.tcag.ca/variation) is a wellknown database.…”

Section: Introductionmentioning

confidence: 99%

Practical guidelines for interpreting copy number gains detected by high-resolution array in routine diagnostics

et al. 2011

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The correct interpretation of copy number gains in patients with developmental delay and multiple congenital anomalies is hampered by the large number of copy number variations (CNVs) encountered in healthy individuals. The variable phenotype associated with copy number gains makes interpretation even more difficult. Literature shows that inheritence, size and presence in healthy individuals are commonly used to decide whether a certain copy number gain is pathogenic, but no general consensus has been established. We aimed to develop guidelines for interpreting gains detected by array analysis using array CGH data of 300 patients analysed with the 105K Agilent oligo array in a diagnostic setting. We evaluated the guidelines in a second, independent, cohort of 300 patients. In the first 300 patients 797 gains of four or more adjacent oligonucleotides were observed. Of these, 45.4% were de novo and 54.6% were familial. In total, 94.8% of all de novo gains and 87.1% of all familial gains were concluded to be benign CNVs. Clinically relevant gains ranged from 288 to 7912 kb in size, and were significantly larger than benign gains and gains of unknown clinical relevance (Po0.001). Our study showed that a threshold of 200 kb is acceptable in a clinical setting, whereas heritability does not exclude a pathogenic nature of a gain. Evaluation of the guidelines in the second cohort of 300 patients revealed that the interpretation guidelines were clear, easy to follow and efficient.

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Transmitted cytogenetic abnormalities in patients with mental retardation: Pathogenic or normal variants?

Cited by 41 publications

References 38 publications

Bohring–Opitz (Oberklaid–Danks) syndrome: clinical study, review of the literature, and discussion of possible pathogenesis

Bohring–Opitz (Oberklaid–Danks) syndrome: clinical study, review of the literature, and discussion of possible pathogenesis

The introduction of arrays in prenatal diagnosis: A special challenge

Practical guidelines for interpreting copy number gains detected by high-resolution array in routine diagnostics

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