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- MR, mental retardation
- XLMR, X linked mental retardation
- MRXS, syndromal X linked mental retardation
- MRX, non-specific X linked mental retardation
- SHS, Sutherland-Haan syndrome
- AR androgen receptor
- RENS1, Renpenning syndrome
X linked mental retardation (XLMR) is classically divided into syndromal (MRXS) and non-specific (MRX) forms, depending on the presence or absence of specific distinguishing clinical, morphological, neurological, or metabolic anomalies. In the last XLMR update1 (http:/xlmr.interfree.it), genetic loci have been assigned for 117 of 202 XLMR by linkage studies, of which only 33 genes have been cloned. From these data, several forms of both syndromal (MRXS) and non-specific mental retardation (MRX) remain without a gene(s) associated disease.1 Moreover, several allelic disorders have been described for some individual cloned genes, reflecting the heterogeneous functional role of a single XLMR associated gene. For instance, molecular defects on the zinc finger/helicase XNP/ATR-X gene,2, 3 the proteolipid protein (PLP), 4 and neuronal cell adhesion molecule L15 (MIM 308840) have been associated with distinct clinical entities. Recently, the MECP2 gene (MIM 300005) responsible for Rett syndrome (MIM 312750) has been shown to account for about 2% of MRX.6
In recent years, cloning and molecular characterisation of XLMR syndromes have provided an increase in the number of these disorders, also as a result of the “lumping together” of allelic syndromes. From this viewpoint, the delineation of specific clinical characteristics accompanying a syndromal form of XLMR would allow the description of a sufficient number of subjects, leading to more accurate genetic counselling, and consequently the identification of the disease associated gene.
We report here the clinical findings and linkage analysis of a family with five mentally retarded males. Examination showed the pedigree to be consistent with an X linked recessive mode of inheritance. Affected males were characterised by a mild form of MR associated with microcephaly and spastic diplegia. All obligate female carriers exhibited a totally skewed pattern of X chromosome inactivation (>90:10).
X chromosome linkage analysis maps the gene …