| Disease entity | Gene | Variant (c.; p.) | Variant type | Evidence/notes (founder, segregation, functional) | Reported in (paper, year) | URL |
|---|---|---|---|---|---|---|
| Temtamy syndrome (C12orf57-related) | C12orf57 | c.1A>G; p.Met1? / p.M1V | Start-loss / initiator codon variant | Homozygous in multiple consanguineous Arab families; segregated with disease under AR inheritance; absent from >1,400 exomes and ethnically matched controls in Akizu; recurrent in Arab patients and suggested founder effect; functional data show AUG→GUG can still initiate translation but with markedly reduced protein levels; 2024 ASD study again found the homozygous variant in affected brothers (pqac-00000019, pqac-00000020, pqac-00000024, pqac-00000049, pqac-00000057, pqac-00000058) | Akizu et al., 2013; Platzer et al., 2014; Al-Sarraj et al., 2024; Alfiya et al., 2022 | https://doi.org/10.1016/j.ajhg.2013.02.004; https://doi.org/10.1002/ajmg.a.36592; https://doi.org/10.3389/fgene.2024.1363849; https://doi.org/10.1007/s12041-022-01371-0 |
| Temtamy syndrome (C12orf57-related) | C12orf57 | c.3G>C; p.Met1Ile | Start-loss / start-codon variant | Novel homozygous variant in a Chinese boy; segregated with AR inheritance and full penetrance in pedigree; predicted to abolish translation / cause loss of function; expanded ethnic spectrum beyond predominantly Middle Eastern cases (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000041) | Wang et al., 2020 | https://doi.org/10.3892/etm.2019.8183 |
| Temtamy syndrome (C12orf57-related) | C12orf57 | c.184C>T; p.Gln62* | Nonsense / stop-gain | Novel nonsense allele reported in trans with c.1A>G in two siblings from nonconsanguineous German parents; compound heterozygous loss-of-function genotype confirmed by parental studies; associated with severe ID, callosal hypoplasia, chorioretinal coloboma, and intractable seizures (pqac-00000031, pqac-00000032, pqac-00000035, pqac-00000039) | Platzer et al., 2014 | https://doi.org/10.1002/ajmg.a.36592 |
| Temtamy syndrome (C12orf57-related) | C12orf57 | c.C43T; p.Q15X | Nonsense / stop-gain | Premature stop codon; reported as compound heterozygous with c.1A>G in a South Indian child; Sanger-confirmed in proband and parents; interpreted as truncating loss-of-function under ACMG framework (pqac-00000005, pqac-00000017, pqac-00000034, pqac-00000037, pqac-00000058) | Alfiya et al., 2022 | https://doi.org/10.1007/s12041-022-01371-0 |
| Temtamy preaxial brachydactyly syndrome (TPBS) | CHSY1 | c.14delG; p.G5AfsX30 | Frameshift | Homozygous LOF allele in TPBS families; cosegregated with autosomal recessive disease; predicted truncation / nonfunctional protein (pqac-00000009, pqac-00000013) | Li et al., 2010 | https://doi.org/10.1016/j.ajhg.2010.10.003 |
| Temtamy preaxial brachydactyly syndrome (TPBS) | CHSY1 | c.55-84del30; p.G19_L28del | In-frame deletion | Reported exon 1 pathogenic deletion in TPBS; part of recurrent CHSY1 loss-of-function spectrum in consanguineous families; absent from controls in original study (pqac-00000008, pqac-00000011, pqac-00000013) | Li et al., 2010 | https://doi.org/10.1016/j.ajhg.2010.10.003 |
| Temtamy preaxial brachydactyly syndrome (TPBS) | CHSY1 | c.205C>T; p.Q69X | Nonsense | Protein-truncating LOF allele identified in TPBS families with AR segregation; supports CHSY1 haploinsufficiency is not mechanism, but biallelic loss is pathogenic (pqac-00000008, pqac-00000009, pqac-00000013) | Li et al., 2010 | https://doi.org/10.1016/j.ajhg.2010.10.003 |
| Temtamy preaxial brachydactyly syndrome (TPBS) | CHSY1 | c.321-3C>G | Splice-site | Acceptor splice variant causing exon 2 skipping, frameshift and premature truncation; strong functional evidence for loss of function (pqac-00000009) | Li et al., 2010 | https://doi.org/10.1016/j.ajhg.2010.10.003 |
| Temtamy preaxial brachydactyly syndrome (TPBS) | CHSY1 | c.1616C>G; p.P539R | Missense | Affects highly conserved residue in CHSY1; interpreted as deleterious and disruptive of protein function; part of pathogenic CHSY1 spectrum in TPBS (pqac-00000009, pqac-00000012) | Li et al., 2010 | https://doi.org/10.1016/j.ajhg.2010.10.003 |
| Temtamy preaxial brachydactyly syndrome (TPBS) | CHSY1 | c.1897G>A; p.D633N | Missense | Homozygous in Pakistani family; parents heterozygous carriers; absent in 100 matched controls; alters conserved Asp633 within DXD motif required for glycosyltransferase activity, supporting enzymatic loss of function (pqac-00000010, pqac-00000012, pqac-00000066, pqac-00000072) | Sher & Naeem, 2014 | https://doi.org/10.1016/j.ejmg.2013.11.001 |


*Table: This table summarizes key pathogenic variants reported for the two distinct entities often called Temtamy syndrome: C12orf57-related Temtamy syndrome and CHSY1-related Temtamy preaxial brachydactyly syndrome. It highlights variant class, segregation, founder evidence, and functional support using only the gathered evidence snippets.*