ORPHA: 808; DO: 0070010;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 13q12.12-q12.13 | ?Seckel syndrome 4 | 613676 | Autosomal recessive | 3 | CENPJ | 609279 |
A number sign (#) is used with this entry because of evidence that Seckel syndrome-4 (SCKL4) is caused by homozygous mutation in the CENPJ gene (609279) on chromosome 13q12. One such family has been reported.
Homozygous mutations in the CENPJ gene can also cause primary microcephaly-6 (MCPH6; 608393).
Seckel syndrome is a rare autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, severe microcephaly with mental retardation, and specific dysmorphic features (Faivre et al., 2002).
For a general description and a discussion of genetic heterogeneity of Seckel syndrome, see 210600.
Al-Dosari et al. (2010) described a consanguineous Saudi family in which several members had clinical features of Seckel syndrome. The proposita had intrauterine growth retardation (IUGR), severe failure to thrive, microcephaly, receding chin, high forehead, prominent nasal spine, hypoplastic alae nasi, and low-set ears; she did not have cognitive and motor development delay or skeletal anomalies. Her sister had IUGR, microcephaly, and the same facial features, but her skeletal survey showed 11 ribs and steep acetabular roof. The sibs had 3 cousins who had short stature, microcephaly, and the same facial features but only 1 of them had intellectual impairment.
Consanguinity and affected sibs in the family with Seckel syndrome reported by Al-Dosari et al. (2010) were consistent with autosomal recessive inheritance.
By homozygosity mapping and linkage analysis in a Saudi family with Seckel syndrome, Al-Dosari et al. (2010) mapped the locus for the disorder to chromosome 13q12 (maximum lod of 3.4).
In affected members of a Saudi family segregating Seckel syndrome, Al-Dosari et al. (2010) identified a homozygous splicing mutation in the last nucleotide of intron 11 of the CENPJ gene (IVS11-1G-C; 609279.0004). The mutation fully segregated with the phenotype in the family and was not found in 96 Saudi controls. Reverse transcription revealed that this splice junction mutation completely abolishes the consensus splice acceptor site and decreases the efficiency of the 2 adjacent acceptor sites, leading to segregation of 3 different transcripts.
Al-Dosari, M. S., Shaheen, R., Colak, D., Alkuraya, F. S. Novel CENPJ mutation causes Seckel syndrome. J. Med. Genet. 47: 411-414, 2010. [PubMed: 20522431] [Full Text: https://doi.org/10.1136/jmg.2009.076646]
Faivre, L., Le Merrer, M., Lyonnet, S., Plauchu, H., Dagoneau, N., Campos-Xavier, A. B., Attia-Sobol, J., Verloes, A., Munnich, A., Cormier-Daire, V. Clinical and genetic heterogeneity of Seckel syndrome. Am. J. Med. Genet. 112: 379-383, 2002. [PubMed: 12376940] [Full Text: https://doi.org/10.1002/ajmg.10677]