Routine diagnosis of DiGeorge syndrome by fluorescent in situ hybridization

Desmaze, Chantal; Scambler, Peter J.; Prieur, M; Halford, Stephanie; Dahi, Sidi; Deist, Françoise Le; Aurias, Alain

doi:10.1007/bf00202489

Cited by 59 publications

(33 citation statements)

References 5 publications

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“…Hence, as previously suggested, FISH should not be used as the only diagnostic method for 22q11.2DS. 39 The phenotypic heterogeneity in 22q11.2DS might be because of (1) the various sizes of the deletions and/or (2) rearrangements elsewhere on the genome -especially CNVs, mutations in candidate genes and changes in the three-dimensional structure of the genome that can lead to dysregulation of gene expression. Zeitz et al 40 found that longrange interactions in the COMT gene had an impact on phenotypic variability.…”

Section: Discussionmentioning

confidence: 99%

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

Poirsier¹,

Besseau-Ayasse²,

Schluth-Bolard³

et al. 2015

Eur J Hum Genet

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Although 22q11.2 deletion syndrome (22q11.2DS) is the most recurrent human microdeletion syndrome associated with a highly variable phenotype, little is known about the condition's true incidence and the phenotype at diagnosis. We performed a multicenter, retrospective analysis of postnatally diagnosed patients recruited by members of the Association des Cytogénéticiens de Langue Française (the French-Speaking Cytogeneticists Association). Clinical and cytogenetic data on 749 cases diagnosed between 1995 and 2013 were collected by 31 French cytogenetics laboratories. The most frequent reasons for referral of postnatally diagnosed cases were a congenital heart defect (CHD, 48.6%), facial dysmorphism (49.7%) and developmental delay (40.7%). Since 2007 (the year in which array comparative genomic hybridization (aCGH) was introduced for the routine screening of patients with intellectual disability), almost all cases have been diagnosed using FISH (96.1%). Only 15 cases (all with an atypical phenotype) were diagnosed with aCGH; the deletion size ranged from 745 to 2904 kb. The deletion was inherited in 15.0% of cases and was of maternal origin in 85.5% of the latter. This is the largest yet documented cohort of patients with 22q11.2DS (the most commonly diagnosed microdeletion) from the same population. French cytogenetics laboratories diagnosed at least 108 affected patients (including fetuses) per year from among a national population of ∼ 66 million. As observed for prenatal diagnoses, CHDs were the most frequently detected malformation in postnatal diagnoses. The most common CHD in postnatal diagnoses was an isolated septal defect.

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Section: Discussionmentioning

confidence: 99%

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

Poirsier¹,

Besseau-Ayasse²,

Schluth-Bolard³

et al. 2015

Eur J Hum Genet

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“…Fluorescent in situ hybridization was performed as previously described (37). Plasmid pPR55 was labeled with biotin-11-dUTP (Sigma) using the nick translation mix (Boehringer Mannheim) according to the supplier.…”

Section: Strainsmentioning

confidence: 99%

Cloning and characterization of hOGG1 , a human homolog of the OGG1 gene of Saccharomyces cerevisiae

Radicella

Dhérin

Desmaze

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

563

305

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The OGG1 gene of Saccharomyces cerevisiae encodes a DNA glycosylase activity that is a functional analog of the Fpg protein from Escherichia coli and excises 7,8-dihydro-8-oxoguanine (8-oxoG) from damaged DNA. The repair of this ubiquitous kind of oxidative damage is essential to prevent mutations both in bacteria and in yeast. A human cDNA clone carrying an ORF displaying homology to the yeast protein was identified. The predicted protein has 345 amino acids and a molecular mass of 39 kDa. This protein shares a 38% sequence identity with the yeast Ogg1 protein, adding this novel human gene product to the growing family of enzymes that the repair of oxidatively damaged bases and are related to the E. coli endonuclease III. Northern blot analysis indicates that this gene, localized to chromosome 3p25, is ubiquitously expressed in human tissues. The cloned coding sequence was expressed in an E. coli strain that carried a disrupted fpg gene, the bacterial functional analog of OGG1. Cell-free extracts from these cultures displayed a specific lyase activity on duplex DNA that carried an 8-oxoG͞C base pair. The products of the reaction are consistent with an enzymatic activity like the one displayed by the yeast Ogg1. Analysis of the substrate specificity reveals a very strong preference for DNA fragments harboring 8-oxoG͞C base pairs. The pattern of specificity correlates well with the one found for the yeast enzyme. Moreover, when the human coding sequence was expressed in a yeast strain mutant in OGG1 it was able to complement the spontaneous mutator phenotype. These results make this novel gene (hOGG1) a strong candidate for the human homolog of the yeast OGG1 and suggest an important role of its product in the protection of the genome from the mutagenic effects of the oxidatively damaged purines.Reactive oxygen species (ROS) formed in cells either as by-products of aerobic metabolism or as a consequence of exposure to environmental mutagens can attack DNA or its precursors, yielding oxidatively damaged bases and strand breakage (1, 2). Unrepaired oxidative damage to DNA has been suggested to play a role in carcinogenesis and aging through mutations in genes controlling these biological processes (3-5). Several lines of evidence suggest that an oxidatively damaged form of guanine, 7,8-dihydro-8-oxoguanine (8-oxoG), is critical in terms of mutagenesis (6, 7). In Escherichia coli, two DNA glycosylases cooperate to prevent mutagenesis by 8-oxoG: the Fpg protein, which excises 8-oxoG in damaged DNA (8-10) and the MutY protein, which excises the adenine residues incorporated by DNA polymerases opposite 8-oxoG (11-13). Inactivation of both the fpg (mutM) and mutY (micA) genes of E. coli results in a strong G⅐C 3 T⅐A mutator phenotype (14-17).In Saccharomyces cerevisiae, the OGG1 gene encodes an 8-oxoG DNA glycosylase activity that reduces the mutator phenotype of the fpg mutY mutant of E. coli (18). The Ogg1 protein contains 376 amino acids, and, although it was cloned by functional complementation of the E. co...

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“…Recently, several studies have suggested that genetic and epigenetic factors exhibit a role in phenotypic variance (2,3,7). Phenotypic variability is often observed between unrelated or related individuals or twins with the same microdeletion syndrome, such as 22q11.2 (3,(8)(9)(10). Observation of the genetic history of a syndrome in MZs often leads to a greater understanding of the phenotypic variability (11).…”

Section: Introductionmentioning

confidence: 99%

Smith‑Magenis syndrome in monozygotic twin fetuses presenting with discordant phenotypes and uteroplacental insufficiency

et al. 2015

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Abstract. Smith-Magenis syndrome (SMS) is a rare condition with multiple congenital malformations caused by the haploinsufficiency of RAI1 (deletion or mutation of RAI1). However, the correlation between genotype and phenotype is not well understood. The present study describes the prenatal diagnosis of monozygotic twins with a 17p11.2 deletion, which is indicative of SMS, who presented with discordant phenotypes and uteroplacental insufficiency. A high-resolution genome-wide single nucleotide polymorphism array revealed a 3.7-Mb deletion in the 17p11.2 chromosome region. Accurate breakpoints of the deletion in these patients were used to identify correlations between SMS and the concomitant phenotypes, particularly uteroplacental insufficiency, which has rarely been investigated in SMS. In addition, no exonic mutations were identified in or affected known disease-associated loci that could explain the congenital anomalies, according to a model that accounts for the possibility of incomplete penetrance. Furthermore, a novel benign copy number variation (a duplication of 195 kb at 13q12.13) was identified but was unlikely to be clinically significant in the discordant phenotypes of the twins. The present study showed that multiple interacting genetic and environmental factors are involved in determining the variance of the SMS phenotype.

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Routine diagnosis of DiGeorge syndrome by fluorescent in situ hybridization

Cited by 59 publications

References 5 publications

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

Cloning and characterization of hOGG1 , a human homolog of the OGG1 gene of Saccharomyces cerevisiae

Smith‑Magenis syndrome in monozygotic twin fetuses presenting with discordant phenotypes and uteroplacental insufficiency

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