Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta

Caron, Véronique; Chassaing, Nicolas; Ragge, Nicola; Boschann, Felix; Ngu, Angelina My-Hoa; Meloche, Elisabeth; Chorfi, Sarah; Lakhani, Saquib A.; Ji, Weizhen; Steiner, Laurie A.; Marcadier, Julien L.; Jansen, Philip R.; Pol, Laura A. van de; Hagen, Johanna M. van; Russi, Alvaro Serrano; Guyader, Gwenaël Le; Nordenskjöld, Magnus; Nordgren, Ann; Anderlid, Britt‐Marie; Plaisancié, Julie; Stoltenburg, Corinna; Horn, Denise; Drenckhahn, Anne; Hamdan, Fadi F.; Lefebvre, Mathilde; Attié‐Bitach, Tania; Forey, Peggy; Смирнов, В. В.; Ernould, Françoise; Jacquemont, Marie‐Line; Grotto, Sarah; Alcantud, Alberto; Coret, Alicia; Ferrer-Avargues, Rosario; Srivastava, Siddharth; Vincent-Delorme, Catherine; Romoser, Shelby; Safina, N. A.; Saade, D.; Lupski, James R.; Calame, Daniel G.; Geneviève, David; Chatron, Nicolas; Schluth-Bolard, Caroline; Myers, Kenneth A.; Dobyns, William B.; Calvas, Patrick; Salmon, Caroline; Holt, Richard; Elmslie, Frances; Allaire, Marc; Prigozhin, Daniil M.; Tremblay, André; Michaud, Jacques L.

doi:10.1016/j.gim.2023.100856

Cited by 5 publications

(3 citation statements)

References 39 publications

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“…While some patients with biallelic pathogenic STRA6 variants have the classical phenotype, additional reports of patients with much milder phenotypes including those with non‐syndromic anophthalmia clearly challenge the clinical definition (Table S1). 10–13 Similarly, a recent large cohort of dominant RARB variants revealed a broad spectrum of phenotypes including those with no eye involvement at all even though this was a consistent finding in nearly all earlier reports 14 . The two families we report in this study similarly demonstrate the highly variable phenotype associated with pathogenic WNT7B variants.…”

Section: Discussionsupporting

confidence: 88%

“…[10][11][12][13] Similarly, a recent large cohort of dominant RARB variants revealed a broad spectrum of phenotypes including those with no eye involvement at all even though this was a consistent finding in nearly all earlier reports. 14 The two families we report in this study similarly demonstrate the highly variable phenotype associated with pathogenic WNT7B variants. Even though both families share the same founder variant, we note that one family displays many PDAC features while the other's phenotype is largely limited to the genitourinary tract.…”

Section: Discussionsupporting

confidence: 65%

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A founder variant expands the phenotype of WNT7B‐related PDAC syndrome

AlAbdi,

Rahbeeni,

Maddirevula

et al. 2024

Clinical Genetics

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Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia, and Cardiac defects (PDAC) syndrome is a genetically heterogeneous multiple congenital malformation syndrome. Although pathogenic variants in RARB and STRA6 are established causes of PDAC, many PDAC cases remain unsolved at the molecular level. Recently, we proposed biallelic WNT7B variants as a novel etiology based on several families with typical features of PDAC syndrome albeit with variable expressivity. Here, we report three patients from two families that share a novel founder variant in WNT7B (c.739C > T; Arg247Trp). The phenotypic expression of this variant ranges from typical PDAC features to isolated genitourinary anomalies. Similar to previously reported PDAC‐associated WNT7B variants, this variant was found to significantly impair WNT7B signaling activity further corroborating its proposed pathogenicity. This report adds further evidence to WNT7B‐related PDAC and expands its variable expressivity.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 65%

A founder variant expands the phenotype of WNT7B‐related PDAC syndrome

AlAbdi,

Rahbeeni,

Maddirevula

et al. 2024

Clinical Genetics

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast, the study of rare genetic variation has only just begun. An explosion of neurodevelopmental disease-gene associations has resulted from family-based studies, next generation sequencing, and online gene matchmaking [ 4 , [111] , [112] , [113] , [114] , [115] , [116] , [117] , [118] , [119] , [120] , [121] , [122] , [123] , [124] , [125] , [126] , [127] , [128] ], but genome-wide functional annotation requires greater international integration of human genomic and phenotypic data. National programs like UK Biobank and All of Us represent an important step in this direction [ 129 , 130 ], but a wealth of genomic and phenotypic data remains locked away in data silos: research databases, clinical diagnostic laboratories, and electronic health records.…”

Section: Functional Genomics Of Mitochondrial Neurodevelopmental Diso...mentioning

confidence: 99%