The oculoauriculofrontonasal syndrome: Further clinical characterization and additional evidence suggesting a nontraditional mode of inheritance

Daphne Lehalle; Umut Altunoglu; Ange-Line Bruel; Mirna Assoum; Yannis Duffourd; Alice Masurel; Geneviève Baujat; Bettina Bessieres; Guillaume Captier; Patrick Edery; Nursel Elçioğlu; David Geneviève; Alice Goldenberg; Delphine Heron; Sarah Grotto; Sandrine Marlin; Audrey Putoux; Massimiliano Rossi; Pascale Saugier-Veber; Stéphane Triau; Christelle Cabrol; Myriam Vezain; Catherine Vincent-Delorme; Christel Thauvin-Robinet; Julien Thevenon; Pierre Vabres; Patrick Callier; Hulya Kayserili; Laurence Faivre

doi:10.1002/ajmg.a.40662

The oculoauriculofrontonasal syndrome: Further clinical characterization and additional evidence suggesting a nontraditional mode of inheritance

Daphne Lehalle ^{1, 2, 3, *} Umut Altunoglu ⁴ Ange-Line Bruel ^{2, 3} Mirna Assoum ^{2, 3} Yannis Duffourd ^{2, 3} Alice Masurel ¹ Geneviève Baujat ⁵ Bettina Bessieres ⁶ Guillaume Captier ⁷ Patrick Edery ^{8, 9} Nursel Elçioğlu David Geneviève ¹⁰ Alice Goldenberg ¹¹ Delphine Heron ^{12, 13} Sarah Grotto ¹¹ Sandrine Marlin ¹⁴ Audrey Putoux ^{8, 9} Massimiliano Rossi ^{8, 9} Pascale Saugier-Veber ¹⁵ Stéphane Triau ¹⁶ Christelle Cabrol ¹⁷ Myriam Vezain ¹⁵ Catherine Vincent-Delorme ¹⁸ Christel Thauvin-Robinet ^{1, 2, 3} Julien Thevenon ^{1, 2, 3} Pierre Vabres ^{2, 3, 19} Patrick Callier ^{2, 3} Hulya Kayserili ²⁰ Laurence Faivre ^{1, 2, 3, *}

* Auteur correspondant

1 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)

2 Equipe GAD (LNC - U1231)

LNC - Lipides - Nutrition - Cancer [Dijon - U1231]

3 UBFC - Université Bourgogne Franche-Comté [COMUE]

4 Departement of Genetics [University of Istanbul]

5 IMAGINE - U1163 - Imagine - Institut des maladies génétiques

6 Laboratoire Histologie Embryologie Cytogénétique [CHU Necker]

7 Département de chirurgie infantile [CHRU de Montpellier]

8 CRNL - Centre de recherche en neurosciences de Lyon

9 Centre de références des syndromes malformatifs et anomalies du développement [CHU Lyon]

10 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)

11 Service de génétique [Rouen]

12 CHU Pitié-Salpêtrière [APHP]

13 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute

14 Inserm U781 - Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement

15 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques

16 Service de foetopathologie (CHU d'Angers)

17 CHRU Besançon - Centre Hospitalier Régional Universitaire [Besançon]

18 Service de génétique clinique (CHU Lille)

19 Service de Dermatologie (CHU de Dijon)

20 Istanbul University

Abstract : The oculoauriculofrontonasal syndrome (OAFNS) is a rare disorder characterized by the association of frontonasal dysplasia (widely spaced eyes, facial cleft, and nose abnormalities) and oculo-auriculo-vertebral spectrum (OAVS)-associated features, such as preauricular ear tags, ear dysplasia, mandibular asymmetry, epibulbar dermoids, eyelid coloboma, and costovertebral anomalies. The etiology is unknown so far. This work aimed to identify molecular bases for the OAFNS. Among a cohort of 130 patients with frontonasal dysplasia, accurate phenotyping identified 18 individuals with OAFNS. We describe their clinical spectrum, including the report of new features (micro/anophtalmia, cataract, thyroid agenesis, polymicrogyria, olfactory bulb hypoplasia, and mandibular cleft), and emphasize the high frequency of nasal polyps in OAFNS (56%). We report the negative results of ALX1, ALX3, and ALX4 genes sequencing and next-generation sequencing strategy performed on blood-derived DNA from respectively, four and four individuals. Exome sequencing was performed in four individuals, genome sequencing in one patient with negative exome sequencing result. Based on the data from this series and the literature, diverse hypotheses can be raised regarding the etiology of OAFNS: mosaic mutation, epigenetic anomaly, oligogenism, or nongenetic cause. In conclusion, this series represents further clinical delineation work of the rare OAFNS, and paves the way toward the identification of the causing mechanism.

Keywords : Oculoauriculofrontonasal syndrome frontonasal dysplasia whole exome sequencing whole genome sequencing

Type de document :

Article dans une revue

Domaine :

Sciences du Vivant [q-bio] / Génétique / Génétique humaine

Liste complète des métadonnées

https://hal-univ-bourgogne.archives-ouvertes.fr/hal-02005698
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : lundi 4 février 2019 - 11:24:47
Dernière modification le : mardi 19 novembre 2019 - 02:42:46

The oculoauriculofrontonasal syndrome: Further clinical characterization and additional evidence suggesting a nontraditional mode of inheritance

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