Candidate genes of oculo‐auriculo‐vertebral spectrum in 22q region: A systematic review

Abstract

Oculo-auriculo-vertebral spectrum (hemifacial microsomia/OAVS, OMIM #164210) is a heterogenous and congenital condition caused by a morphogenesis defect of the first and second pharyngeal arches. Etiology includes unknown genetic, environmental factors and chromosomal alterations, which 22q11.2 region is the most frequently reported. Several candidate genes for OAVS have been proposed; however, none has been confirmed as causative of the phenotype. This review aims to sum up all clinical and molecular findings in 22q region of individuals diagnosed with OAVS and to investigate genes that may be involved in the development of the spectrum. A search was performed in PubMed using all entry terms to OAVS and Chromosome 22q11. After screening, 11 papers were eligible for review. Deletions and duplications in the q11.2 region were the most frequent (18/22) alterations reported and a total of 68 genes were described. Our systematic review reinforces the hypothesis that 22q11 region is a candidate locus for OAVS as well as CLTCL1, GSC2, HIRA, MAPK1, TBX1, and YPEL1 as potential candidates genes for genotype-phenotype correlation. Complementary studies regarding genes interaction involved in the 22q11 region are still necessary in the search for a genotype-phenotype association, since the diagnosis of OAVS is a constant medical challenge.

De novo 22q11.2 deletions and auricular findings in two Chinese patients with microtia

“…In both cases in the present study, distinct malformed pinna was noticed, including enlarged auricular cranial angle, lacking antihelix, triangular fossa, scapha, antitragus, and malformed tragus and ear lobe. Hemifacial macrosomia (HMF) is also suggested as one of the minimum diagnostic criteria for OAVS patients with 22q11 abnormalities (Glaeser et al, 2020). Accordingly, we observed slight facial asymmetry in patient 1 and downturned corners of the mouth and anteverted nares, although these facial features are not as apparent as the malformed pinna.…”

“…In OAVS patients, recurrent genomic alterations in chromosome 22q were reported. Glaeser et al reviewed the clinical characterization in 22 patients with OAVS in chromosome 22 abnormalities and reported the detailed auricular alterations in these patients (Glaeser et al, 2020). Kruszka also reported 59% (53/90) ear anomalies in 22q11.2 DS patients (Kruszka et al, 2017).…”

“…Besides, those cases with proximal deletion were detected by FISH using a limited probe, thus making the extent of the deletion hardly known. Previous studies mainly focused on two candidate genes within the 22q11.2 proximal region, the TBX1 and GSC2 (Glaeser et al, 2020). TBX1 is closely related to retinoic acid (RA) signaling, while GSC2 is implicated in the development of neural crestderived structures (Glaeser et al, 2020;Guris et al, 2006).…”

“…Previous studies mainly focused on two candidate genes within the 22q11.2 proximal region, the TBX1 and GSC2 (Glaeser et al, 2020). TBX1 is closely related to retinoic acid (RA) signaling, while GSC2 is implicated in the development of neural crestderived structures (Glaeser et al, 2020;Guris et al, 2006). Nonetheless, no causal relationship has been established between these two genes and ear malformation due to heterogeneous phenotypes and limited cases with mutations only affecting the candidate gene.…”

Yippee Like 1 Suppresses Glioma Progression and Serves as a Novel Prognostic Factor

“…Yippee Like 1 (YPEL1) gene was initially cloned by Farlie et al (2001) from embryonic mice, which was later mapped in human chromosome 22q11.2, a region associated with several congenital anomalies involving craniofacial malformation, including DiGeorge syndrome and velocardiofacial syndrome (Hosono et al 2004). Dysregulated YPEL1 may also be correlated with development of oculoauriculo-vertebral spectrum (hemifacial microsomia/OAVS) (Glaeser et al 2020), a heterogenous and congenital condition caused by a morphogenesis defect of the first and second pharyngeal arches. YPEL1 protein contains a putative nuclear localization sequence, and located in the centrosome and nucleolus, thus may play a role in the regulation of cell division.…”