Alternative titles; symbols
HGNC Approved Gene Symbol: CCNQ
SNOMEDCT: 723581006;
Cytogenetic location: Xq28 Genomic coordinates (GRCh38): X:153,587,925-153,599,139 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| Xq28 | STAR syndrome | 300707 | X-linked dominant | 3 |
Unger et al. (2008) identified the FAM58A gene in an analysis of genomic deletions in individuals with a constellation of facial dysmorphism and malformations designated STAR syndrome (300707). The 642-bp coding region encodes a protein of 214 amino acids. Using EST data, the authors found expression of the FAM58A gene in 27 of 48 adult tissues including kidney, colon, cervix, and uterus, but not heart. Genes homologous to FAM58A were found on the X chromosome in chimpanzee and dog; in mouse and rat, no true homologs were found. FAM58A contains a cyclin box-fold domain, a protein-binding domain found in cyclins with a role in cell cycle and transcription control. Coimmunoprecipitation assays demonstrated that FAM58A interacts with SALL1 (602218) but not SALL4 (607343), suggesting that FAM58A and SALL1 participate in the same developmental pathway. Knockdown of FAM58A mRNA by RNA interference (RNAi) in HEK293 cells resulted in a significant reduction of both FAM58A mRNA expression and proliferation of transfected cells.
Unger et al. (2008) determined that the FAM58A gene has 5 coding exons.
FAM58A is located approximately 0.56 Mb centromeric to MECP2 (300005) on chromosome Xq28 (Unger et al., 2008).
In 2 females with anogenital and renal malformations, dysmorphic facial features, normal intelligence, and syndactyly of toes (STAR; 300707), Unger et al. (2008) detected heterozygous genomic deletions removing regions of the FAM58A gene (300708.0001-300708.0002). In 4 additional affected females, including the mother-daughter pair reported by Green et al. (1996), the authors identified heterozygous point mutations in FAM58A (300708.0003-300708.0005).
In a 19-year-old woman with STAR syndrome, Lefroy et al. (2017) identified a heterozygous deletion of the FAM58A gene. Her mother, who had only bilateral 4-5 toe syndactyly, was found to have approximately 50% mosaicism for the same deletion.
In a girl (case 1) with STAR syndrome (STAR; 300707) and additional features of lower lid coloboma, epilepsy, and syringomyelia, Unger et al. (2008) identified a de novo heterozygous deletion on chromosome Xq28 of approximately 40 kb (g.152,514,164_152,554,231del, NCBI36) that removed exons 1 and 2 as well as intron 1, a portion of intron 2, and the 5-prime untranslated region of the FAM58A gene.
In a girl (case 3) with STAR syndrome (STAR; 300707), Unger et al. (2008) detected a de novo heterozygous deletion of 4,249 bp (g.152,504,123_152,508,371del, NCBI36), which removed 1,265 bp of intron 4, all of exon 5 including the 3-prime untranslated region of the FAM58A gene, and 2,454 bp of 3-prime sequence.
In a girl (case 2) with STAR syndrome (STAR; 300707), Unger et al. (2008) identified a heterozygous donor splice site mutation (c.555+1G-A) in intron 4 of the FAM58A gene.
In a girl (case 4) with STAR syndrome (STAR; 300707), Unger et al. (2008) identified a heterozygous 1-bp duplication (c.201dupT) in the FAM58A gene, resulting in a frameshift and a premature stop codon (Asn68TerfsTer1).
In the mother and daughter (cases 5 and 6), previously reported by Green et al. (1996), with STAR syndrome (STAR; 300707), Unger et al. (2008) identified a heterozygous c.555-1G-A mutation in the FAM58A gene, which altered the splice acceptor site of intron 4.
Green, A. J., Sandford, R. N., Davison, B. C. C. An autosomal dominant syndrome of renal and anogenital malformations with syndactyly. J. Med. Genet. 33: 594-596, 1996. [PubMed: 8818947] [Full Text: https://doi.org/10.1136/jmg.33.7.594]
Lefroy, H., Hurst, J. A., Shears, D. J. STAR syndrome: a further case and the first report of maternal mosaicism. Clin. Dysmorph. 26: 157-160, 2017. [PubMed: 28225384] [Full Text: https://doi.org/10.1097/MCD.0000000000000176]
Unger, S., Bohm, D., Kaiser, F. J., Kaulfuss, S., Borozdin, W., Buiting, K., Burfeind, P., Bohm, J., Barrionuevo, F., Craig, A., Borowski, K., Keppler-Noreuil, K., and 9 others. Mutations in the cyclin family member FAM58A cause an X-linked dominant disorder characterized by syndactyly, telecanthus and anogenital and renal malformations. Nature Genet. 40: 287-289, 2008. [PubMed: 18297069] [Full Text: https://doi.org/10.1038/ng.86]