Mental Retardation, X-Linked 9

A number sign (#) is used with this entry because this form of nonspecific X-linked mental retardation is caused by mutation in the FTSJ1 gene (300499).

Clinical Features

Nonspecific X-linked mental retardation (MRX) includes several distinct entities with mental retardation but without additional distinguishing features.

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.

Mapping

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.

Molecular Genetics

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).