Table A1.
Summary of all variants and results of Sanger sequencing (includes variants not presented in Table 3).
| Subject | Scale of Variant | Gene Name and Location | Variant Type | Encoded Protein | Signaling Pathways/Neuronal Circuitry | Other Conditions Associated with the Variant | Mutation Confirmed by Sanger? |
|---|---|---|---|---|---|---|---|
| #2 | Small | GJB2 (chr13:20189473:C:T) | Missense | Connexin 26, CX26 (gap junction protein, beta 2) | Calcium Signaling Pathway | Hearing impairment; Keratitis-ichthyosis-deafness syndrome, autosomal dominant; Mutilating keratoderma; genetic deafness | Yes |
| #2 | Small | PROKR2 (chr20:5302662:C:G) | Missense | Prokineticin receptor 2 | Mood regulation; Gonadotropin-releasing hormone; Neutrophil dependent inflammation; Hyper nociception; Migration of nerve cells; Neurogenesis |
Kallmann syndrome 3 | No |
| #2 | Large |
PWRN1 in 15q11.2 (chr15:24521630:A:G) |
Deletion-Duplication | N.A. | N.A. | N.A. | N.A. |
| #3 | Small |
PROP1 (chr5:177995888:G:A) |
Stop gained | Paired-like homeodomain transcription factor | Retinoic acid production and signaling pathway; Regulates neuronal excitability |
Pituitary hormone deficiency, combined | Yes |
| #3 | Small |
CYP11B1 (chr8:142874995:G:A) |
Missense | Enzyme: 11-beta-hydroxylase | Non identified | Adrenal hyperplasia; congenital Hyperaldosteronism, familial, type I | Yes |
| #3 | Small |
MRE11 (chr11:94459461:G:A) |
Stop gained | Double Strand Break Repair Nuclease | DNA damage signaling; Chromatin stability |
Hereditary cancer-predisposing syndrome; Ataxia-telangiectasia-like disorder 1 | N.A. |
| #3 | Large |
POLR3E in 16p12.1 (chr16:22305383:GA:G) |
Deletion-Duplication | DNA-directed RNA polymerase III subunit RPC5 | RNA Polymerase III Transcription Initiation; Transcription of tRNA. May be important for fighting CNS viral infection |
N.A. | N.A. |
| #4 | Small | SLC7A14 (chr3:170480891:C:A) | Missense | Glycosylated, cationic amino acid transporter protein with 14 transmembrane domains | Full-length 771-amino acid SLC7A14 protein has 14 transmembrane domains and an N-glycosylation site in extracellular loop-2 | Retinitis pigmentosa | Yes |
| #4 | Small | GJB2 (chr13:20189473:C:T) | Missense | Connexin 26, CX26 (gap junction protein, beta 2) | Calcium Signaling Pathway | Hearing impairment | Yes |
| #4 | Small | TXNL4A (chr11:94459461:G:A) | Intron | DIM1, U5 snRNP-SPECIFIC PROTEIN, a member of the U5 small ribonucleoprotein particle (snRNP) | Spliceosome pathway | Burn-McKeown syndrome | N.A. |
| #5 | Small | USH2A (chr1:216078088:C:T) | Splice donor | Usherin | USH protein network pathway | Usher syndrome, type 2A; Retinitis pigmentosa 39 | N.A. |
| #5 | Small | SERPINB7 (chr18:63798670:C:CT) | Frameshift | SERPINB7 | Degradation of SERPINB7 protein by 26S proteasome-mediated pathway | Palmoplantar keratoderma, nagashima type | Yes |
| #5 | Small | BSCL2 (chr11:62692671:C:A) | Missense & NMD transcript | Seipin | Critical in pathway of adipogenesis; Affect neurogenesis in hypothalamus; May be involved in hypothalamic pituitary gland axis function |
Charcot-Marie-Tooth disease, type 2; Congenital generalized lipodystrophy type 2 | No |
| #5 | Large |
MRNIP in 5q35 (chr5:179858784:G:A) |
Duplication | MRN- interacting protein | N.A. | N.A. | |
| #6 | Small | MYOC (chr1:171652476:G:A) | Splice region variant & intron variant & NMD transcript variant | Myocilin | Modulator of Wnt signaling pathway; Wild-type MYOC inhibits activation of the IL-1/NF-κB pathway |
Glaucoma | Yes |
| #6 | Small | SLCO1B1 (chr12:21196975:C:T) | Stop gained | Organic anion transporting polypeptide 1B1 | Liver-specific member of the organic anion transporter family | Gilbert syndrome; Rotor syndrome | No |