Alternative titles; symbols
ORPHA: 777; DO: 0112034;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xp11.23 | Intellectual developmental disorder, X-linked 9 | 309549 | X-linked recessive | 3 | FTSJ1 | 300499 |
A number sign (#) is used with this entry because of evidence that X-linked intellectual developmental disorder-9 (XLID9) is caused by mutation in the FTSJ1 gene (300499).
X-linked intellectual developmental disorder-9 (XLID9) is characterized by moderately to severely impaired intellectual development. Some patients have also been reported with delayed motor development, seizures, and/or behavioral problems (Hamel et al., 1999; Froyen et al., 2007).
Hamel et al. (1999) described a 4-generation family segregating X-linked mental retardation. Affected members had nonprogressive mental retardation noted during childhood, and several demonstrated aggressive behavior. The mental retardation in tested members of the family was moderate to severe; none of the patients was able to read, write, or solve simple arithmetic problems.
Froyen et al. (2007) reported 3 Caucasian brothers with nonsyndromic X-linked mental retardation. Two had moderate and 1 had severe intellectual handicap. The oldest patient had autistic behavior that lessened after age 5 years, as well as delayed speech and motor development. The 2 younger brothers also had seizures; 1 had flat nasal bridge and shortened distal phalanges. High-resolution array CGH identified a 50-kb microdeletion at Xp11.23 involving the FTSJ1 and SLC38A5 (300649) genes. Detailed mapping studies suggested that the deletion breakpoints involved the repeat region of the SSX1 gene (312820). The unaffected mother also carried the deletion, but showed complete inactivation of the aberrant X chromosome. Froyen et al. (2007) concluded that the cognitive impairment in this family was most likely due to absence of the FTSJ1 gene.
Willems et al. (1993) described linkage studies in a family classified as MRX9 in the nomenclature proposed by Mulley et al. (1992) and reviewed by Neri et al. (1992). The studies suggested localization in the pericentromeric region, namely, Xp21-q13. Winnepenninckx et al. (2002) restudied the Belgian family reported by Willems et al. (1993) and refined the mapping of the MRX9 gene to Xp11.4-p11.22.
Hamel et al. (1999) performed linkage analysis in family MRX44 and obtained a maximum lod score of 2.90 (theta = 0.0) with marker DXS1204. Haplotype construction defined the region to Xp11.3-p11.21, spanning an approximately 10-cM interval flanked by markers DXS1003 and ALAS2.
The MRX44 family of Hamel et al. (1999) was shown by Freude et al. (2004) to carry a mutation in the FTSJ1 gene (300499.0001), resulting in deletion of exon 9.
In the Belgian MRX9 family reported by Willems et al. (1993), Ramser et al. (2004) established a gene catalog for the candidate region defined by Winnepenninckx et al. (2002). Comprehensive mutation analysis by direct sequencing identified an alteration in the conserved acceptor splice site of intron 3 of the FTSJ1 gene (300499.0004).
Freude, K., Hoffmann, K., Jensen, L.-R., Delatycki, M. B., des Portes, V., Moser, B., Hamel, B., van Bokhoven, H., Moraine, C., Fryns, J.-P., Chelly, J., Gecz, J., Lenzner, S., Kalscheuer, V. M., Ropers, H.-H. Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding protein cause nonsyndromic X-linked mental retardation. Am. J. Hum. Genet. 75: 305-309, 2004. [PubMed: 15162322] [Full Text: https://doi.org/10.1086/422507]
Froyen, G., Bauters, M., Boyle, J., van Esch, H., Govaerts, K., van Bokhoven, H., Ropers, H.-H., Moraine, C., Chelly, J., Fryns, J.-P., Marynen, P., Gecz, J., Turner, G. Loss of SLC38A5 and FTSJ1 at Xp11.23 in three brothers with non-syndromic mental retardation due to a microdeletion in an unstable genomic region. Hum. Genet. 121: 539-547, 2007. [PubMed: 17333282] [Full Text: https://doi.org/10.1007/s00439-007-0343-1]
Hamel, B. C. J., Smits, A. P. T., van den Helm, B., Smeets, D. F. C. M., Knoers, N. V. A. M., van Roosmalen, T., Thoonen, G. H. J., Assman-Hulsmans, C. F. C. H., Ropers, H.-H., Mariman, E. C. M., Kremer, H. Four families (MRX43, MRX44, MRX45, MRX52) with nonspecific X-linked mental retardation: clinical and psychometric data and results of linkage analysis. Am. J. Med. Genet. 85: 290-304, 1999. [PubMed: 10398246]
Mulley, J. C., Kerr, B., Stevenson, R., Lubs, H. Nomenclature guidelines for X-linked mental retardation. Am. J. Med. Genet. 43: 383-391, 1992. [PubMed: 1605216] [Full Text: https://doi.org/10.1002/ajmg.1320430159]
Neri, G., Chiurazzi, P., Arena, F., Lubs, H. A., Glass, I. A. XLMR genes: update 1992. Am. J. Med. Genet. 43: 373-382, 1992. [PubMed: 1605215] [Full Text: https://doi.org/10.1002/ajmg.1320430158]
Ramser, J., Winnepenninckx, B., Lenski, C., Errijgers, V., Platzer, M., Schwartz, C. E., Meindl, A., Kooy, R. F. A splice site mutation in the methyltransferase gene FTSJ1 in Xp11.23 is associated with non-syndromic mental retardation in a large Belgian family (MRX9). J. Med. Genet. 41: 679-683, 2004. [PubMed: 15342698] [Full Text: https://doi.org/10.1136/jmg.2004.019000]
Willems, P., Vits, L., Buntinx, I., Raeymaekers, P., Van Broeckhoven, C., Ceulemans, B. Localization of a gene responsible for nonspecific mental retardation (MRX9) to the pericentromeric region of the X chromosome. Genomics 18: 290-294, 1993. [PubMed: 8288232] [Full Text: https://doi.org/10.1006/geno.1993.1468]
Winnepenninckx, B., Errijgers, V., Reyniers, E., De Deyn, P. P., Abidi, F. E., Schwartz, C. E., Kooy, R. F. Family MRX9 revisited: further evidence for locus heterogeneity in MRX. Am. J. Med. Genet. 112: 17-22, 2002. [PubMed: 12239714] [Full Text: https://doi.org/10.1002/ajmg.10663]