ORPHA: 808; DO: 0070012;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 15q21.1 | Seckel syndrome 5 | 613823 | Autosomal recessive | 3 | CEP152 | 613529 |
A number sign (#) is used with this entry because Seckel syndrome-5 is caused by homozygous or compound heterozygous mutation in the CEP152 gene (613529) on chromosome 15q21.
Seckel syndrome is an autosomal recessive disorder characterized by proportionate short stature, severe microcephaly, mental retardation, and a typical 'bird-head' facial appearance (summary by Kalay et al., 2011).
For a general phenotypic description and a discussion of genetic heterogeneity of Seckel syndrome, see 210600.
Kalay et al. (2011) clinically evaluated 5 consanguineous families with Seckel syndrome originating from an isolated rural area in Turkey. The patients presented with microcephaly, sloping forehead, high nasal bridge, beaked nose, and retrognathia. Cranial magnetic resonance imaging in 2 patients showed simplified gyri.
Seckel syndrome-5 is an autosomal recessive disorder (Kalay et al., 2011).
Using SNP array homozygosity mapping in 4 affected members of 3 Turkish families segregating Seckel syndrome, Kalay et al. (2011) obtained a lod score of 6.03 on chromosome 15q21.1-q21.2. Subsequent fine mapping confirmed shared homozygosity and a founder haplotype in a 3.4-Mb region between markers D15S123 and D15S1017.
Kalay et al. (2011) sequenced the candidate gene CEP152 in affected members of 3 Turkish families segregating Seckel syndrome mapping to chromosome 15q21.1-q21.2 and identified a homozygous splice site mutation in intron 4 (613529.0003), which cosegregated with the founder haplotype. Through the use of an exome sequencing strategy, Kalay et al. (2011) identified the same mutation in an affected French individual of Turkish origin, who was born to consanguineous parents. By sequence analysis, Kalay et al. (2011) also identified compound heterozygous mutations in the CEP152 gene in affected Seckel syndrome patients of different ethnic origins (613529.0004-613529.0007).
Kalay, E., Yigit, G., Aslan, Y., Brown, K. E., Pohl, E., Bicknell, L. S., Kayserili, H., Li, Y., Tuysuz, B., Nurnberg, G., Kiess, W., Koegl, M., and 20 others. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nature Genet. 43: 23-26, 2011. [PubMed: 21131973] [Full Text: https://doi.org/10.1038/ng.725]