Prenatal detection of TAR syndrome in a fetus with compound inheritance of an RBM8A SNP and a 334-kb deletion: A case report

Papoulidis, Ioannis; Oikonomidou, Eirini; Orrù, Sandro; Siomou, Elisavet; Kontodiou, Maria; Eleftheriades, Makarios; Bacoulas, Vasilios; Cigudosa, Juan C.; Suela, Javier; Thomaidis, Loretta; Manolakos, Emmanouil

doi:10.3892/mmr.2013.1788

Cited by 20 publications

(18 citation statements)

References 8 publications

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“…An enlargement of the deleted region is provided in the lower panel. A similar deletion was observed in case 11, whose array profile is illustrated in Papoulidis et al; B, Copy number profile of chromosome 1 from both cases as analyzed by EXCAVATOR ; C, IGV screenshot shows the c.‐ 21G >A variant of RMB8A in both cases (in green, arrows). Grey bars represent the mapped reads aligned to the reference genome, whose sequence is shown in the bottom (colored letters).…”

Section: Methodssupporting

confidence: 53%

“…Cases 1, 11 and 12 were prenatally diagnosed because of ultrasound abnormalities. Cases 3, 4‐6, 11, 13, 15, and 17 have been previously described . Relevant data are available at DECIPHER (https://decipher.sanger.ac.uk/index, see Table ).…”

Section: Methodsmentioning

confidence: 99%

“…Conventional capillary sequencing was applied in cases 11 to 15 and 17, by using standard methods to analyze the gene/s of interest, as reported elsewhere . Primers and PCR conditions are available on request.…”

Section: Methodsmentioning

confidence: 99%

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Diagnostic application of a capture based NGS test for the concurrent detection of variants in sequence and copy number as well as LOH

et al. 2017

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Whole exome sequencing (WES) has made the identification of causative SNVs/InDels associated with rare Mendelian conditions increasingly accessible. Incorporation of softwares allowing CNVs detection into the WES bioinformatics pipelines may increase the diagnostic yield.However, no standard protocols for this analysis are so far available and CNVs in non-coding regions are totally missed by WES, in spite of their possible role in the regulation of the flanking genes expression. So, in a number of cases the diagnostic workflow contemplates an initial investigation by genomic arrays followed, in the negative cases, by WES. The opposite workflow may also be applied, according to the familial segregation of the disease.We show preliminary results for a diagnostic application of a single next generation sequencing panel permitting the concurrent detection of LOH and variations in sequences and copy number. This approach allowed us to highlight compound heterozygosity for a CNV and a sequence variant in a number of cases, the duplication of a non-coding region responsible for sex reversal, and a whole-chromosome isodisomy causing reduction to homozygosity for a WFS1 variant. Moreover, the panel enabled us to detect deletions, duplications, and amplifications with sensitivity comparable to that of the most widely used array-CGH platforms. K E Y W O R D Scopy number variations, exome sequencing, genetic diagnosis, isodisomy, loss of heterozygosity

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Section: Methodssupporting

confidence: 53%

Section: Methodsmentioning

confidence: 99%

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Diagnostic application of a capture based NGS test for the concurrent detection of variants in sequence and copy number as well as LOH

et al. 2017

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“…, and with thrombocytopenia-absent radius syndrome (OMIM 274000) due to a deletion in the RBM8A gene [Papoulidis et al, 2014]. Phenotypically normal carriers have also been reported [Mefford et al, 2008].…”

mentioning

confidence: 99%

Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability

et al. 2016

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We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A, DUF1220, and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date.

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“…Following the identification of the two SNPs, at least 22 new TAR cases have been reported (Omran et al , ; Bottillo et al , ; Baken et al , ; Idahosa et al , ; Papoulidis et al , ; Reid et al , ; Yassaee et al , ; Al Kaissi et al , ; Kumar et al , ,b; Pereira et al , ; Tassano et al , ; Nicchia et al , ; Jameson‐Lee et al , ). However, the presence of the microdeletion on chromosome 1q21.1 or of the hemizygous SNPs has not been reported in more than half of the described patients (Omran et al , ; Baken et al , ; Idahosa et al , ; Reid et al , ; Al Kaissi et al , ; Kumar et al , ; Pereira et al , ).…”

Section: Diagnosis/differential Diagnosesmentioning

confidence: 99%

Impact of genetic variants on haematopoiesis in patients with thrombocytopenia absent radii (TAR) syndrome

et al. 2017

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Thrombocytopenia absent radii (TAR) syndrome is clearly defined by the combination of radial aplasia and reduced platelet counts. The genetics of TAR syndrome has recently been resolved and comprises a microdeletion on Chromosome 1 including the RBM8A gene and a single nucleotide polymorphism (SNP) either at the 5' untranslated region (5'UTR) or within the first intron of RBM8A. Although phenotypically readily diagnosed after birth, the genetic determination of particular SNPs in TAR syndrome harbours valuable information to evaluate disease severity and treatment decisions. Here, we present clinical data in a cohort of 38 patients and observed that platelet counts in individuals with 5'UTR SNP are significantly lower compared to patients bearing the SNP in intron 1. Moreover, elevated haemoglobin values could only be assessed in patients with 5'UTR SNP whereas white blood cell count is unaffected, indicating that frequently observed anaemia in TAR patients could also be SNP-dependent whereas leucocytosis does not correlate with genetic background. However, this report on a large cohort provides an overview of important haematological characteristics in TAR patients, facilitating evaluation of the various traits in this disease and indicating the importance of genetic validation for TAR syndrome.

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Prenatal detection of TAR syndrome in a fetus with compound inheritance of an RBM8A SNP and a 334-kb deletion: A case report

Cited by 20 publications

References 8 publications

Diagnostic application of a capture based NGS test for the concurrent detection of variants in sequence and copy number as well as LOH

Diagnostic application of a capture based NGS test for the concurrent detection of variants in sequence and copy number as well as LOH

Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability

Impact of genetic variants on haematopoiesis in patients with thrombocytopenia absent radii (TAR) syndrome

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