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The oculoauriculofrontonasal syndrome: Further clinical characterization and additional evidence suggesting a nontraditional mode of inheritance
Author(s) -
Lehalle Daphné,
Altunoglu Umut,
Bruel AngeLine,
Assoum Mirna,
Duffourd Yannis,
Masurel Alice,
Baujat Geneviève,
Bessieres Bettina,
Captier Guillaume,
Edery Patrick,
Elçioğlu Nursel H.,
Geneviève David,
Goldenberg Alice,
Héron Delphine,
Grotto Sarah,
Marlin Sandrine,
Putoux Audrey,
Rossi Massimiliano,
SaugierVeber Pascale,
Triau Stéphane,
Cabrol Christelle,
Vézain Myriam,
VincentDelorme Catherine,
ThauvinRobinet Christel,
Theve Julien,
Vabres Pierre,
Callier Patrick,
Kayserili Hulya,
Faivre Laurence
Publication year - 2018
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.40662
Subject(s) - exome sequencing , dysplasia , etiology , biology , genetics , medicine , anatomy , pathology , mutation , gene
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.