Localization of the gene (or genes) for a syndrome with X-linked mental retardation, ataxia, weakness, hearing impairment, loss of vision and a fatal course in early childhood

Abstract

Linkage analysis is described in a family with X-linked m ental retardation, ataxia, weakness, floppiness, delayed m otor developm ent, absence of deep tendon re flexes, hearing im pairm ent and loss of vision (M IM no. 301835). The disease has a fatal course due to the suscep tibility of the patients to infections, especially of the res piratory tract. Clinical signs indicate impairment of the posterior columns, peripheral m otor and sensory neurons and the second and eighth cranial nerves and/or their nu clei. The involvem ent of the posterior columns of the spinal cord is further suggested by the almost complete absence of myelinated fibers therein. We localized the re sponsible gene(s) to X q21.33-q24 betw een D X S 1231 and DXS 1001 with a m axim um lod score o f 6.97. The proteolipid protein gene, which codes for two myelin proteins of the central nervous system and is located in this region, was considered as a candidate gene for this disorder. However, no m utations were found in the protein-coding part of this gene.

A novel gene, tendin, is strongly expressed in tendons and ligaments and shows high homology with chondromodulin‐I

“…Arts syndrome has been mapped to Xq21.33‐q24 where tendin is also located (Arts et al, 1993; Kremer et al, 1996). Male newborns with Arts syndrome show an early‐onset floppiness and the development of ataxia, areflexia, flaccid tetraplegia, and myelin loss in the posterior columns of the spinal cord.…”

A Novel Ribosomal S6-Kinase (RSK4; RPS6KA6) Is Commonly Deleted in Patients with Complex X-Linked Mental Retardation

“…Affected males of 200 families were tested, 16 of which had a genetic defect linked to Xq21. Some of these families have been described: MRX4 (Hu et al, 1994), MRX13 (Kerr et al, 1992), MRX20 (Lazzarini et al, 1995), MRX52 , MRX65 (Yntema et al, 1999), Wilson-Turner syndrome (Wilson et al, 1991), MR with ataxia and deafness (Kremer et al, 1996), and MR with cleft palate and short stature (Hamel et al, 1994).…”

Hearing loss andPRPS1mutations: Wide spectrum of phenotypes and potential therapy

“…Up to 80% of reported patients with Arts syndrome died before age six, primarily from infectious complications. The oldest patient, then 16 years of age, was nearly blind due to optic atrophy, and lived in an institution for the visually and mentally handicapped (Kremer et al, 1996). Two loss-of-function mutations of the PRPS1 gene have been identified, c.455T> C (p.L152P) in the original Dutch kindred, and c.398A > C (p.Q133P) in the Australian family.…”