ORPHA: 808; DO: 0070006;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3q22.2 | ?Seckel syndrome 6 | 614728 | Autosomal recessive | 3 | CEP63 | 614724 |
A number sign (#) is used with this entry because of evidence that Seckel syndrome-6 (SCKL6) is caused by homozygous mutation in the CEP63 gene (614724) on chromosome 3q22. One such family has been reported.
For a general phenotypic description and a discussion of genetic heterogeneity of Seckel syndrome, see SCKL1 (210600).
Sir et al. (2011) ascertained a consanguineous Pakistani family in which 3 female cousins were born with microcephaly, with head circumferences of -4 SD to -6 SD. All had speech delay, but learned to speak by 3 years of age; by age 5 years there was clear evidence of cognitive delay, but there was no motor delay. At the time of examination they were 18 years, 16 years, and 7.5 years of age, and all had head circumferences of 9 to 15 cm below the 3rd centile. All 3 had short stature, with heights that ranged from -2 SD to -4 SD. There was no history of seizures, and there were no other malformations.
In 3 affected female cousins from a consanguineous Pakistani family with microcephaly and short stature, Sir et al. (2011) performed autozygosity mapping and identified a single 24-Mb locus of homozygosity on chromosome 3, between markers D3S3513 at 137 cM and D3S1569 at 158 cM.
The transmission pattern of SCKL6 in the family reported by Sir et al. (2011) was consistent with autosomal recessive inheritance.
In 3 female cousins from a consanguineous Pakistani family with microcephaly and short stature mapping to chromosome 3q22, Sir et al. (2011) sequenced 3 candidate genes and identified homozygosity for a nonsense mutation in the CEP63 gene (W43X; 614724.0001).
Sir, J.-H., Barr, A. R., Nicholas, A. K., Carvalho, O. P., Khurshid, M., Sossick, A., Reichelt, S., D'Santos, C., Woods, C. G., Gergely, F. A primary microcephaly protein complex forms a ring around parental centrioles. Nature Genet. 43: 1147-1153, 2011. [PubMed: 21983783] [Full Text: https://doi.org/10.1038/ng.971]