ORPHA: 1466, 191; DO: 0080912;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19q13.32 | ?Cerebrooculofacioskeletal syndrome 2 | 610756 | Autosomal recessive | 3 | ERCC2 | 126340 |
A number sign (#) is used with this entry because of evidence that cerebrooculofacioskeletal syndrome-2 (COFS2) is caused by compound heterozygous mutation in the DNA repair gene XPD (ERCC2; 126340) on chromosome 19q13. One such patient has been reported.
For a phenotypic description and a discussion of genetic heterogeneity of cerebrooculofacioskeletal syndrome, see 214150.
Graham et al. (2001) described a patient with COFS syndrome who was the child of nonconsanguineous Ashkenazi Jewish parents. At birth, examination showed severe intrauterine growth deficiency, microcephaly, deep-set small eyes with bilateral cataracts, prominent beaked nose, micrognathia, micropenis with scrotal hypoplasia, finger contractures with a simian crease on the right, kyphoscoliosis, and rocker-bottom feet. At the age of 13 months, he was noted to be profoundly delayed in growth and development, with sparse hair and a deeply sunburned face suggesting cutaneous photosensitivity. The patient had severe microcephaly with extensive joint contractures, required repeated hospital admissions, and died at the age of 3.5 years. Skin fibroblasts showed sensitivity to UV radiation to a degree comparable to that in patients with severe xeroderma pigmentosum of complementation group A. Restoration of NER activity occurred after fusion with cells from XPB and XPG but not after fusion with cells from XPD patients.
In a child with COFS, Graham et al. (2001) found compound heterozygosity for 2 mutations in the ERCC2 gene: a novel asp681-to-asn (D681N) mutation (126340.0009), and an arg616-to-trp null mutation (126340.0010), which had previously been observed in patients with xeroderma pigmentosum complementation group D (278730). Graham et al. (2001) proposed that patients with ultraviolet-sensitive COFS syndrome be included within the spectrum of individuals with impaired nucleotide-excision repair (NER) disorders.
Graham, J. M., Jr., Anyane-Yeboa, K., Raams, A., Appeldoorn, E., Kleijer, W. J., Garritsen, V. H., Busch, D., Edersheim, T. G., Jaspers, N. G. J. Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy. Am. J. Hum. Genet. 69: 291-300, 2001. [PubMed: 11443545] [Full Text: https://doi.org/10.1086/321295]