ORPHA: 124; DO: 0111897;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xp11.22 | ?Diamond-Blackfan anemia 14 with mandibulofacial dysostosis | 300946 | X-linked recessive | 3 | TSR2 | 300945 |
A number sign (#) is used with this entry because of evidence that Diamond-Blackfan anemia-14 with mandibulofacial dysostosis (DBA14) is caused by hemizygous mutation in the TSR2 gene (300945) on chromosome Xp11. One such family has been reported.
For a discussion of genetic heterogeneity of DBA, see DBA1 (105650).
Gripp et al. (2001) reported 2 boys, related as maternal first cousins, with bilateral microtia and cleft palate associated with Diamond-Blackfan anemia. The patients had microtia with absent external auditory canals, conductive hearing loss, micrognathia, midface hypoplasia, downslanting palpebral fissures, and sparse eyelashes on the medial lower lid. One patient had submucous cleft palate and unilateral cryptorchidism; the other had cleft palate. Neither patient had abnormalities of the radial rays. One of them had a sister with hematologic findings of Diamond-Blackfan anemia. Physical examination of the mothers showed no abnormalities, and the fathers were reportedly unaffected.
Gripp et al. (2014) reported that both male cousins reported by Gripp et al. (2001) were in good health at 24 and 16 years of age.
The transmission pattern of DBA14 in the family with mandibulofacial dysostosis reported by Gripp et al. (2001, 2014) was consistent with X-linked recessive inheritance.
In 2 male first cousins with DBA14 with mandibulofacial dysostosis originally reported by Gripp et al. (2001), Gripp et al. (2014) identified a hemizygous missense mutation in the TSR2 gene (E64G; 300945.0001). The mutation, which was found by sequencing of candidate ribosomal protein genes, segregated with the disorder in the family. Functional studies of the variant were not performed, but Gripp et al. (2014) noted that TSR2 is involved in processing and maturation of rRNA and binds to RPS26 (603701), which is mutated in Diamond-Blackfan anemia-10 (DBA10; 613309).
Exclusion Studies
By sequence analysis, Gripp et al. (2001) found no mutation in the RPS19 gene (603474) on chromosome 19, which is the site of the gene defect in autosomal dominant Diamond-Blackfan anemia (105650). Also, Gripp et al. (2001) reported that no linkage was found to markers at 8p23, to which a locus for Diamond-Blackfan anemia had been mapped (see 606129). Gripp et al. (2001) concluded that microtia, cleft palate, and Diamond-Blackfan anemia is a distinct syndrome that is not allelic to known Diamond-Blackfan anemia loci.
Gripp, K. W., Curry, C., Olney, A. H., Sandoval, C., Fisher, J., Chong, J. X.-L., UW Center for Mendelian Genomics, Pilchman, L., Sahraoui, R., Stabley, D. L., Sol-Church, K. Diamond-Blackfan anemia with mandibulofacial dystostosis (sic) is heterogeneous, including the novel DBA genes TSR2 and RPS28. Am. J. Med. Genet. 164A: 2240-2249, 2014. [PubMed: 24942156] [Full Text: https://doi.org/10.1002/ajmg.a.36633]
Gripp, K. W., McDonald-McGinn, D. M., La Rossa, D., McGain, D., Federman, N., Vlachos, A., Glader, B. E., McKenzie, S. E., Lipton, J. M., Zackai, E. H. Bilateral microtia and cleft palate in cousins with Diamond-Blackfan anemia. Am. J. Med. Genet. 101: 268-274, 2001. [PubMed: 11424144] [Full Text: https://doi.org/10.1002/ajmg.1329]