A novel missense variant of the GNAI3 gene and recognisable morphological characteristics of the mandibula in ARCND1

• Published in: Journal of human genetics 2021-10, Vol.66 (10), p.1029-1034
• Main Authors: Yanagi, Kumiko, Morimoto, Noriko, Iso, Manami, Abe, Yukimi, Okamura, Kohji, Nakamura, Tomoo, Matsubara, Yoichi, Kaname, Tadashi
• Format: Article
• Language: English
• Subjects: Binding sites; Brief Communication; Child, Preschool; Ear - abnormalities; Ear - diagnostic imaging; Ear - pathology; Ear Diseases - diagnosis; Ear Diseases - diagnostic imaging; Ear Diseases - genetics; Ear Diseases - pathology; Female; GTP-Binding Protein alpha Subunits, Gi-Go - genetics; Guanine; Guanine nucleotide-binding protein; Humans; Hypoplasia; Mandible; Mandible - diagnostic imaging; Mandible - pathology; Micrognathism - diagnosis; Micrognathism - diagnostic imaging; Micrognathism - genetics; Micrognathism - pathology; Mutation, Missense - genetics; Pedigree; Phenotype; Physical characteristics; Sequence analysis; Whole Exome Sequencing
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/s10038-021-00915-z

Auriculocondylar syndrome (ARCND) is an autosomal monogenic disorder characterised by external ear abnormalities and micrognathia due to hypoplasia of the mandibular rami, condyle and coronoid process. Genetically, three subtypes of ARCND (ARCND1, ARCND2 and ARCND3) have been reported. To date, five pathogenic variants of GNAI3 have been reported in ARCND1 patients. Here, we report a novel variant of GNAI3 (NM_006496:c.807C>A:p.(Asn269Lys)) in a Japanese girl with micrognathia using trio-based whole exome sequencing analysis. The GNAI3 gene encodes a heterotrimeric guanine nucleotide-binding protein. The novel variant locates the guanine nucleotide-binding site, and the substitution was predicted to interfere with guanine nucleotide-binding by in silico structural analysis. Three-dimensional computer tomography scan, or cephalogram, displayed severely hypoplastic mandibular rami and fusion to the medial and lateral pterygoid plates, which have been recognised in other ARCND1 patients, but have not been described in ARCND2 and ARCND3, suggesting that these may be distinguishable features in ARCND1.