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

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...

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Bibliographic Details
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
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Description
Summary: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.
ISSN:1434-5161
1435-232X
DOI:10.1038/s10038-021-00915-z