TAR syndrome: Clinical and molecular characterization of a cohort of 26 patients and description of novel noncoding variants of
            <i>RBM8A</i>

Boussion, Simon; Escande, Fabienne; Jourdain, Anne‐Sophie; Smol, Thomas; Brunelle, Perrine; C, Duhamel; Alembik, Yves; Attié‐Bitach, Tania; Baujat, Geneviève; Bazin, Anne; Bonnière, Maryse; Carassou, P.; Carles, Dominique; Devisme, Louise; Goizet, Cyril; Goldenberg, Alice; Grotto, Sarah; Guichet, Agnès; Jouk, Pierre‐Simon; Lœuillet, Laurence; Mechler, Charlotte; Michot, Caroline; Pelluard, Fanny; Putoux, Audrey; Whalen, Sandra; Ghoumid, Jamal; Manouvrier‐Hanu, Sylvie; Petit, Florence

doi:10.1002/humu.24021

Cited by 22 publications

(27 citation statements)

References 34 publications

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“…This hypomorphic variant was recently reported in the literature, mainly in individuals with African ancestry. 6 Since the Brazilian population is highly admixed, with a signifi- ES elucidated the diagnosis of syndromes recently reported or still under delineation in three individuals, two of them without a clear diagnostic hypothesis. In acrofacial dysostosis Cincinnati type, the same heterozygous variant in POLR1A was previously identified in a Brazilian girl, inherited from her mildly affected father.…”

Section: Discussionmentioning

confidence: 99%

Congenital limb deficiency: Genetic investigation of 44 individuals presenting mainly longitudinal defects in isolated or syndromic forms

et al. 2021

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Congenital limb deficiency (CLD), one of the most common congenital anomalies, is characterized by hypoplasia/aplasia of one or more limb bones and can be isolated or syndromic. The etiology in CLD is heterogeneous, including environmental and genetic factors. A fraction remains with no etiological factor identified. We report the study of 44 Brazilian individuals presenting isolated or syndromic CLD, mainly with longitudinal defects. Genetic investigation included particularly next-generation sequencing (NGS) and/or chromosomal microarray. The overall diagnostic yield was 45.7%, ranging from 60.9% in the syndromic to 16.7% in the non-syndromic group.In TAR syndrome, a common variant in 3´UTR of RBM8A, in trans with 1q21.1 microdeletion, was detected, corroborating the importance of this recently reported variant in individuals of African ancestry. NGS established a diagnosis in three individuals in syndromes recently reported or still under delineation (an acrofacial dysostosis, Coats plus and Verheij syndromes), suggesting a broader phenotypic spectrum in these disorders. Although a low rate of molecular detection in non-syndromic forms was observed, it is still possible that variants in non-coding regions and small CNVs, not detected by the techniques applied in this study, could play a role in the etiology of CLD.

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Section: Discussionmentioning

confidence: 99%

Congenital limb deficiency: Genetic investigation of 44 individuals presenting mainly longitudinal defects in isolated or syndromic forms

et al. 2021

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“…It is noteworthy that several DECIPHER patients with polydactyly and other hand, foot, ulna, radius, or metacarpal bone anomalies are associated with heterozygous deletions involving FAT1 , some inherited from a healthy parent and others de novo (cases 263566, 263566, 249192, 276704, 273754, 285956, 300330, 384020, 392005, 392006, 392058, 392082, 392076, 392066, 393352, 392845, 394362, 394338, 394314, 394279, 395652, 401296, 398400, 398396). This observation suggests the presence in the non-deleted allele of medium frequency regulatory variants that lower protein production below the minimum level for normal limb embryogenesis, according to the TAR syndrome model [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Whole Exome Sequencing Is the Minimal Technological Approach in Probands Born to Consanguineous Couples

Peluso

Caraffi

Zuntini

et al. 2021

Genes

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We report on two siblings suffering from different pathogenic conditions, born to consanguineous parents. A multigene panel for brain malformations and microcephaly identified the homozygous splicing variant NM_005886.3:c.1416+1del in the KATNB1 gene in the older sister. On the other hand, exome sequencing revealed the homozygous frameshift variant NM_005245.4:c.9729del in the FAT1 gene in the younger sister, who had a more complex phenotype: in addition to bilateral anophthalmia and heart defects, she showed a right split foot with 4 toes, 5 metacarpals, second toe duplication and preaxial polydactyly on the right hand. These features have been never reported before in patients with pathogenic FAT1 variants and support the role of this gene in the development of limb buds. Notably, each parent was heterozygous for both of these variants, which were ultra-rare and rare, respectively. This study raises awareness about the value of using whole exome/genome sequencing rather than targeted gene panels when testing affected offspring born to consanguineous couples. In this way, exomic data from the parents are also made available for carrier screening, to identify heterozygous pathogenetic and likely pathogenetic variants in genes responsible for other recessive conditions, which may pose a risk for subsequent pregnancies.

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“…TAR syndrome is congenital and is diagnosed for low platelet count in early age or reduction of megakaryocytes in the bone marrow. Patients with TAR syndrome often show a wide range of skeletal abnormalities from preserved thumbs, radial anomalies, renal anomalies, lower-limbs anomalies to cow’s milk intolerance [ 162 , 163 , 164 ].…”

Section: Ejc Components Are Implicated In Phenotypically Diverse Gene...mentioning

confidence: 99%

The Physiological Roles of the Exon Junction Complex in Development and Diseases

Asthana

Martin

Rupkey

et al. 2022

Cells

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The exon junction complex (EJC) becomes an increasingly important regulator of early gene expression in the central nervous system (CNS) and other tissues. The EJC is comprised of three core proteins: RNA-binding motif 8A (RBM8A), Mago homolog (MAGOH), eukaryotic initiation factor 4A3 (EIF4A3), and a peripheral EJC factor, metastatic lymph node 51 (MLN51), together with various auxiliary factors. The EJC is assembled specifically at exon-exon junctions on mRNAs, hence the name of the complex. The EJC regulates multiple levels of gene expression, from splicing to translation and mRNA degradation. The functional roles of the EJC have been established as crucial to the normal progress of embryonic and neurological development, with wide ranging implications on molecular, cellular, and organism level function. Dysfunction of the EJC has been implicated in multiple developmental and neurological diseases. In this review, we discuss recent progress on the EJC’s physiological roles.

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TAR syndrome: Clinical and molecular characterization of a cohort of 26 patients and description of novel noncoding variants of RBM8A

Cited by 22 publications

References 34 publications

Congenital limb deficiency: Genetic investigation of 44 individuals presenting mainly longitudinal defects in isolated or syndromic forms

Congenital limb deficiency: Genetic investigation of 44 individuals presenting mainly longitudinal defects in isolated or syndromic forms

Whole Exome Sequencing Is the Minimal Technological Approach in Probands Born to Consanguineous Couples

The Physiological Roles of the Exon Junction Complex in Development and Diseases

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