Table 3.
Synopsis of the genes in which associations were identified in this study.
| Ethnicity/Statistical model/Sex | Type of analysis | Gene ID (location)a | Gene full name | Gene description and additional commentsb | Key references |
|---|---|---|---|---|---|
| Asian; X-inactivation | Single-marker | EGFL6 (Xp22.2) | EGF like domain multiple 6 | EGFL6 is an EGF-repeat containing gene belonging to the EGF-repeat superfamily. Members of this gene family are involved in cell cycle regulation and proliferation. The mouse homolog, Egf16, is strongly expressed in the mesenchymal components of both the hard and soft palate from embryonic stage E12.5. | Buchner et al., 2000a,b |
| FGF13 (Xq26.3-q27.1) | Fibroblast growth factor 13 | FGF13 belongs to the FGF family of signaling molecules—one of the largest growth factor families. FGF signaling is essential to the development of craniofacial structures. Several FGF ligands and receptors are expressed in the developing facial primordia, and mutations in FGF receptors are known to cause different clefting syndromes (e.g. Kallmann and Apert). | Nie et al., 2006; Rahimov et al., 2012; Du et al., 2016 | ||
| DMD (Xp21.2-p21.1) | Dystrophin | Dystrophin is a component of the dystrophin-glycoprotein complex whose function is to provide stability to muscle membranes by bridging the cytoskeleton of the muscle to the extracellular matrix. Mutations in DMD cause Duchenne (DMD) and Becker (BMD) Muscular Dystrophies. Associations between variants in DMD and OFCs have been reported in four chromosome-wide analyses of X-linked SNPs. | Michele and Campbell, 2003; Patel et al., 2013; Fonseca et al., 2015; Wise et al., 2016; Skare et al., 2017 | ||
| Asian; No X-inactivation | Haplotype | DMD (Xp21.2-p21.1) | Dystrophin | As above. | As above. |
| PRPS2 (Xp22.2) | Phosphoribosyl pyrophosphate synthetase 2 | This gene encodes a phosphoribosyl pyrophosphate synthetase that plays a central role in protein and nucleotide biosynthesis. | Cunningham et al., 2014 | ||
| European; No X-inactivation | Single-marker | SPANXN4 (Xq27.3) | SPANX family member N4 | SPANXN4 belongs to the SPANX multigene family of cancer/testis-specific antigens that play important roles in spermiogenesis. | Kouprina et al., 2004 |
| USP26 (Xq26.2) | Ubiquitin specific peptidase 26 | USP26 belongs to a large family of deubiquitinating enzymes and this gene is specifically expressed in testis tissue. Variants in USP26 have been linked to male infertility in some but not all studies. | Stouffs et al., 2005; Wosnitzer et al., 2014; Zhang et al., 2015 | ||
| European; No X-inactivation | Haplotype | ZNF157 (Xp11.3) | Zinc finger protein 157 | ZNF157 belongs to the zinc-finger family of transcription factors. ZNF157 is part of a gene cluster of ZNF genes on chromosome Xp11.23. | Derry et al., 1995 |
| GABRE (Xq28) | Gamma-aminobutyric acid type A receptor epsilon subunit | GABRE encodes the “Gamma-aminobutyric acid type A receptor epsilon subunit.” This gene maps to a cluster on chromosome Xq28 that houses other subunits of the same receptor. Fatemi et al. (2013) reported increased expression of GABRE in the lateral cerebella of subjects with schizophrenia, bipolar disorder and major depressive disorder. | Fatemi et al., 2013 | ||
| Asian; Girls only | Single-marker | EGFL6 (Xp22.2) | EGF like domain multiple 6 | As above. | As above. |
| FGF13 (Xq26.3-q27.1) | Fibroblast growth factor 13 | As above. | As above. | ||
| DMD (Xp21.2-p21.1) | Dystrophin | As above. | As above. | ||
| Asian; Girls only | Haplotype | ITIH6 (Xp11.22) | Inter-alpha-trypsin inhibitor heavy chain family member 6 | ITIH6 encodes a protein belonging to the inter-alpha trypsin inhibitor heavy chain (ITIH) family. Al-Mubarak et al. (2017) performed whole-exome sequencing of autism spectrum disorders (ASD) triads and uncovered rare variants in several X-linked genes, including ITIH6. | Al-Mubarak et al., 2017 |
| FRMPD4 (Xp22.2) | FERM and PDZ domain containing 4 | FRMPD4 encodes a multi-domain (PDZ and FERM) containing protein. It modulates the activity of key postsynaptic scaffold proteins that are involved in cognitive processes. Variants in FRMPD4 have been associated with X-linked intellectual disability and schizophrenia. | Hu et al., 2016; Matosin et al., 2016; Trujillano et al., 2017 | ||
| PRPS2 (Xp22.2) | Phosphoribosyl pyrophosphate synthetase 2 | As above. | As above. |
a
Genes located within the same chromosomal band Xp22.2 are emboldened.
b
Information on these genes was collated from the NCBI Entrez gene database (https://www.ncbi.nlm.nih.gov/gene) and the references shown.