ORPHA: 564; DO: 0070120;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 4p15.32 | Meckel syndrome 6 | 612284 | Autosomal recessive | 3 | CC2D2A | 612013 |
A number sign (#) is used with this entry because Meckel syndrome type 6 (MKS6) is caused by homozygous mutation in the CC2D2A gene (612013) on chromosome 4p15.
For a general phenotypic description and a discussion of genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
Tallila et al. (2008) reported the clinical features of probands from 11 Finnish families with Meckel syndrome. All fetuses had occipital encephalocele and large cystic kidneys. Most also had polydactyly of the hands and feet, clubfeet, fibrotic or cystic changes in the liver, and hypoplastic lungs. Less common features included cleft lip/palate, anencephaly, and gonadal abnormalities. Fibroblasts isolated from 1 fetus showed no detectable cilia, although there was normal cellular localization of centrioles.
The transmission pattern of MKS6 in the families reported by Tallila et al. (2008) was consistent with autosomal recessive inheritance.
By genomewide SNP scan of 10 unrelated Finnish fetuses with Meckel syndrome, Tallila et al. (2008) found homozygosity in 6 for a shared overlapping region on chromosome 4p15. Inbreeding coefficients indicated that none of the 6 fetuses were closely related.
Tallila et al. (2008) selected the CC2D2A gene as a candidate for Meckel syndrome on chromosome 4p15 by searching a ciliary proteome database. Genetic analysis identified a homozygous nonsense mutation in this gene (612013.0002) in affected fetuses from 11 of 17 Finnish families with the disorder. All parents were heterozygous for the mutation. The remaining 6 families did not have CC2D2A mutations. Further analysis of 575 healthy controls indicated that the carrier frequency of the CC2D2A mutation was 0.5% in the Finnish population.
In a patient with Meckel syndrome who was compound heterozygous for mutations in CC2D2A, Kim et al. (2010) identified heterozygosity for a missense mutation in the C2ORF86 gene (613580.0003). Homozygous mutations in C2ORF86 were shown to result in Bardet-Biedl syndrome (see 209900).
Kim, S. K., Shindo, A., Park, T. J., Oh, E. C., Ghosh, S., Gray, R. S., Lewis, R. A., Johnson, C. A., Attie-Bittach, T., Katsanis, N., Wallingford, J. B. Planar cell polarity acts through septins to control collective cell movement and ciliogenesis. Science 329: 1337-1340, 2010. [PubMed: 20671153] [Full Text: https://doi.org/10.1126/science.1191184]
Tallila, J., Jakkula, E., Peltonen, L., Salonen, R., Kestila, M. Identification of CC2D2A as a Meckel syndrome gene adds an important piece to the ciliopathy puzzle. Am. J. Hum. Genet. 82: 1361-1367, 2008. [PubMed: 18513680] [Full Text: https://doi.org/10.1016/j.ajhg.2008.05.004]