Table 1. Complete list of genes with rare pathological/deleterious variants associated with the present case*.
* Gene-to-protein name conversion was performed using the GeneCards database; **BBB: blood brain barrier.
| Gene | Protein function |
| A1BG | Alpha-1-B glycoprotein |
| ABCA3 | ATP binding cassette subfamily A member 3; brain development [18]; progenitor cell regulation; neurogenesis [19]; vesicle transport [20] |
| ABHD5 | Abhydrolase domain containing 5, lysophosphatidic acid acyltransferase; skin barrier defect [21] |
| ACSS1 | Acyl-CoA synthetase short chain family member 1 |
| ADGRA2 | Adhesion G protein-coupled receptor A2; brain development [8]; cerebral angiogenesis [9]; Wnt signaling [22,23]; bifrontal PMG with multiple congenital anomalies [24] |
| ADPRHL1 | ADP-ribosylhydrolase-like 1 ROCK signaling [25] |
| BIRC7 | Baculoviral IAP repeat containing 7 |
| C19orf57 | Break repair meiotic recombinase recruitment factor 1 |
| CAPN12 | Calpain 12; angiogenesis [26]; intellectual disability [27] |
| CARMIL3 | Capping protein regulator and myosin 1 linker 3; brain ischemia [28]; cell migration [29] |
| CCDC198 | Coiled-coil domain containing 198. Neurogenesis; progenitor cell regulation; cell migration [30] |
| CHAF1A | Chromatin assembly factor 1 subunit A. Neurogenesis [31,32] |
| CHRND | Cholinergic receptor nicotinic delta subunit. Neuromuscular junction formation [33] |
| CMPK2 | Cytidine/uridine monophosphate kinase 2 |
| CYP17A1 | Cytochrome P450 family 17 subfamily A member 1; angiogenesis [34] |
| DENND1B | DENN domain containing 1B; vesicle transport [35] |
| DHRS2 | Dehydrogenase/reductase 2 |
| DNAH3 | Dynein axonemal heavy chain 3; motile cilia regulation [36] |
| FLG2 | Filaggrin 2; brain development [37]; skin disease [38] |
| GCC2 | GRIP and coiled-coil domain containing 2 |
| GLYATL3 | Glycine-N-acyltransferase like 3 |
| GUSB | Glucuronidase beta |
| HLA-DRB1 | Major histocompatibility complex, class II, DR beta 1 |
| HLA-DRB5 | Major histocompatibility complex, class II, DR beta 5 |
| HLTF | Helicase-like transcription factor; neurogenesis/brain development [39]; neuronal cell death [40] |
| IFI30 | IFI30 lysosomal thiol reductase; angiogenesis [41]; neuronal cells death [42] |
| JAG2 | Jagged canonical notch ligand 2; progenitor cell regulation [11]; angiogenesis [10] |
| KMT2C | Lysine methyltransferase 2C; neurogenesis/brain development [43,44] |
| KRT19 | Keratin 19 |
| KRT86 | Keratin 86 |
| KRTAP3-2 | Keratin associated protein 3-2 |
| LAMA1 | Laminin subunit alpha 1. Neurogenesis/brain development [12]; angiogenesis [13] |
| LONP1 | Lon Peptidase 1, mitochondrial. Mitochondrial encephalopathy [45]; neuronal cell death [46] |
| LRGUK | Leucine-rich repeats and guanylate kinase domain containing. Motile cilia regulation [47] |
| LRRC58 | Leucine-rich repeat containing 58. Neuroinflammation [48,49] |
| MDH1 | Malate dehydrogenase 1. Energy metabolism [50]; neuronal cell death [51] |
| MGST2 | Microsomal glutathione S-transferase 2. Neuronal cell death [52]; angiogenesis [53] |
| MLXIP | MLX interacting protein. Brain development/neurogenesis; progenitor cell regulation; energy metabolism [54] |
| MPEG1 | Macrophage expressed 1 |
| MRPL57 | Mitochondrial ribosomal protein L57. Energy metabolism [55] |
| MS4A15 | Membrane spanning 4-domains A15. Brain development/neurogenesis [56] |
| MTUS1 | Microtubule-associated scaffold protein 1. Rac signaling [57] |
| MYO7B | Myosin VIIB. Vesicle transport [58]. Possibly linked to brain development/neurogenesis [59] |
| NGLY1 | N-glycanase 1. Brain development/neurogenesis [60,61]; neuronal cell death [62] |
| NMU | Neuromedin U |
| OBSCN | Obscurin, cytoskeletal calmodulin, and titin-interacting. Brain development/neurogenesis [63] |
| OPN3 | Opsin 3 |
| OR2S2 | Olfactory receptor family 2 subfamily S member 2. BBB** regulation [64] |
| PAH | Phenylalanine hydroxylase |
| PCDHA1 | Protocadherin alpha 1. Brain development/neurogenesis [65,66]; Wnt signaling [67] |
| PCDHA12 | Protocadherin alpha 12. Brain development/neurogenesis [68]; Wnt signaling [69,70] |
| PGK2 | Phosphoglycerate kinase 2 |
| PHKB | Phosphorylase kinase regulatory subunit beta |
| PI15 | Peptidase inhibitor 15 |
| PLEKHG3 | Pleckstrin homology and RhoGEF domain containing G3. Brain development/neurogenesis [71,72]; Rho signaling [72]; linked to mild intellectual disability [73] |
| PSG6 | Pregnancy-specific beta-1-glycoprotein 6. Brain development/neurogenesis [74] |
| PTK7 | Protein tyrosine kinase 7 (Inactive). Brain development/neurogenesis [75,76]; Wnt signaling [75,77]; cell migration [77] |
| PTPRN2 | Protein tyrosine phosphatase receptor type N2. TGFβ signaling [78]; cerebral vasculature remodeling [79] |
| RGR | Retinal G protein coupled receptor |
| RIT2 | Ras like without CAAX 2. Brain development/neurogenesis; Ras signaling [80] |
| RSL1D1 | Ribosomal L1 domain containing 1 (cellular senescence-inhibited gene protein, CSIG). Cell proliferation and senescence [81]; linked to child cognitive development [82] |
| SEMA3D | Semaphorin 3D. Signaling [83]; linked to cognitive impairment [14]; angiogenesis [15] |
| SKIV2L | SKI2 subunit of superkiller complex |
| SLC26A1 | Solute carrier family 26 member 1 |
| SLC9C1 | Solute carrier family 9 member C1. Sperm-specific component of motile cilia [84] |
| SYNM | Synemin. Neurogenesis; progenitor cell regulation; cell migration [16] |
| TIAM2 | TIAM Rac1 associated GEF 2. Brain development/neurogenesis; Rho signaling [85] |
| TLN2 | Talin 2 |
| TMEM43 | Transmembrane protein 43 |
| TPGS1 | Tubulin polyglutamylase complex Subunit 1. Cilia regulation [86] |
| TTN | Titin |
| TUT1 | Terminal uridylyl transferase 1, U6 SnRNA-specific. Brain development/neurogenesis [87]; neuronal cell death [88] |
| TYK2 | Tyrosine kinase 2. Brain development/neurogenesis [89]. Jak/Stat signaling; neuronal cell death [90] |
| UBE4B | Ubiquitination factor E4B. Brain development/neurogenesis; progenitor cell regulation; mTOR signaling [91]; neuronal cell death [92] |
| UGT1A7 | UDP glucuronosyltransferase family 1 member A7; BBB regulation [93] |
| UNKL | Unk like zinc finger. Neurogenesis [94] |
| UPK1A | Uroplakin 1A |
| USP4 | Ubiquitin specific peptidase 4. Brain development/neurogenesis [95,96]; neuronal cell death [97]; Wnt signaling [98,99] |
| ZBED9 | SCAN domain containing 3 (SCAND3). Potential biomarker for mild cognitive impairment [100] |
| ZC3H3 | Zinc finger CCCH-type containing 3 |
| ZNF227 | Zinc finger protein 227 |
| ZNF540 | Zinc finger protein 540 |
| ZYX | Zyxin. Brain development/neurogenesis [101]; tight junction/BBB regulation [102]; Shh signaling [103]; cell migration [104] |