HGNC Approved Gene Symbol: FAM111B
Cytogenetic location: 11q12.1 Genomic coordinates (GRCh38) : 11:59,107,237-59,127,412 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 11q12.1 | Poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonary fibrosis | 615704 | Autosomal dominant | 3 |
Mercier et al. (2013) reported that the deduced 734-amino acid FAM111B protein has a C-terminal trypsin-like cysteine/serine peptidase domain that is split into 2 parts by a loop. Microarray and database analyses revealed widespread FAM111B expression.
Mercier et al. (2013) reported that the FAM111B gene contains 4 exons.
Mercier et al. (2013) reported that the FAM111B gene maps to chromosome 11q12.1.
Mercier et al. (2013) stated that FAM111B interacts with polyubiquitin C (UBC; 191340) and ATP13A2 (610513).
In affected individuals from 5 unrelated families with fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP; 615704), who were negative for mutation in the RECQL4 gene (603780), Mercier et al. (2013) identified heterozygosity for missense mutations in the FAM111B gene (615584.0001-615584.0003). The mutations were not found in unaffected parents available for testing or in 388 controls.
In 3 affected sibs from a South African family of European descent with fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP; 615704), originally described by Khumalo et al. (2006), Mercier et al. (2013) identified heterozygosity for a c.1861T-G transversion in exon 4 of the FAM111B gene, resulting in a tyr621-to-asp (Y621D) substitution at a residue conserved in primates. The mutation was not found in the patients' unaffected mother or in 388 controls, including 165 South Africans, 93 of whom were of European origin. DNA was unavailable from the patients' affected father, who died of diffuse interstitial pulmonary fibrosis at age 56 years.
In 3 unrelated probands with fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP; 615704), born to French, Italian, and Algerian parents, respectively, Mercier et al. (2013) identified heterozygosity for a c.1879A-G transition in exon 4 of the FAM111B gene, resulting in an arg627-to-gly (R627G) substitution at a residue conserved across mammalian species. The mutation was confirmed to be de novo in 2 of the families and was not found in 388 controls, including 96 Algerians.
In a 6-year-old girl with fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP; 615704), born of a French mother and Moroccan father, Mercier et al. (2013) identified heterozygosity for a c.1883G-A transition in exon 4 of the FAM111B gene, resulting in a ser628-to-asn (S628N) substitution at a residue conserved across mammalian species. The mutation was not found in 388 controls, including 127 Moroccans.
Khumalo, N. P., Pillay, K., Beighton, P., Wainwright, H., Walker, B., Saxe, N., Mayosi, B. M., Bateman, E. D. Poikiloderma, tendon contracture and pulmonary fibrosis: a new autosomal dominant syndrome? Brit. J. Derm. 155: 1057-1061, 2006. [PubMed: 17034542] [Full Text: https://doi.org/10.1111/j.1365-2133.2006.07473.x]
Mercier, S., Kury, S., Shaboodien, G., Houniet, D. T., Khumalo, N. P., Bou-Hanna, C., Bodak, N., Cormier-Daire, V., David, A., Faivre, L., Figarella-Branger, D., Gherardi, R. K., and 18 others. Mutations in FAM111B cause hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis. Am. J. Hum. Genet. 93: 1100-1107, 2013. [PubMed: 24268661] [Full Text: https://doi.org/10.1016/j.ajhg.2013.10.013]