Strømme, P. et al. X linked mental retardation and infantile spasms in a family: new clinical data and linkage to Xp11.4-Xp22.11. J. Med. Genet. 36, 374−378

Department of Paediatrics, Rikshospitalet, University of Oslo, Norway.
Journal of Medical Genetics (Impact Factor: 6.34). 06/1999; 36(5):374-8. DOI: 10.1136/jmg.36.5.374
Source: PubMed


In order to describe the neurological abnormalities and to identify the gene localisation, we re-evaluated a previously reported family with X linked mental retardation (XLMR). Reliable data were obtained for six of the seven affected males, of whom two had had infantile spasms. Profound MR (IQ<20) was found in one and mild MR (IQ 50-70) in five males. No dysmorphic features, except for macrocephaly in one male, were found. Neurological abnormalities included varying degrees of spinocerebellar involvement. Neuroimaging studies showed abnormalities, such as cerebellar atrophy or corpus callosum hypoplasia or both, in three of the six males. Several affected and unaffected subjects suffered from hyperhidrosis, which appeared to segregate independently as an autosomal dominant trait. Genetic linkage analysis localised the XLMR disease gene to Xp11.4-Xp22.11 with a maximum multipoint lod score of 3.57, overlapping the candidate region recently found in two Belgian XLMR-infantile spasm families. Compared to the Belgian patients, the majority of the affected males in this report had a considerably milder phenotype.

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Available from: Kjetil Sundet, Oct 04, 2015
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    • "The condition was mapped to Xp11.4-p22.11 [84]. "
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    ABSTRACT: X-linked disorders with cerebellar dysgenesis (XLCD) are a genetically heterogeneous and clinically variable group of disorders in which the hallmark is a cerebellar defect (hypoplasia, atrophy or dysplasia) visible on brain imaging, caused by gene mutations or genomic imbalances on the X-chromosome. The neurological features of XLCD include hypotonia, developmental delay, intellectual disability, ataxia and/or other cerebellar signs. Normal cognitive development has also been reported. Cerebellar dysgenesis may be isolated or associated with other brain malformations or multiorgan involvement. There are at least 15 genes on the X-chromosome that have been constantly or occasionally associated with a pathological cerebellar phenotype. 8 XLCD loci have been mapped and several families with X-linked inheritance have been reported. Recently, two recurrent duplication syndromes in Xq28 have been associated with cerebellar hypoplasia. Given the report of several forms of XLCD and the excess of males with ataxia, this group of conditions is probably underestimated and families of patients with neuroradiological and clinical evidence of a cerebellar disorder should be counseled for high risk of X-linked inheritance.
    Orphanet Journal of Rare Diseases 05/2011; 6(1):24. DOI:10.1186/1750-1172-6-24 · 3.36 Impact Factor
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    • "The most frequent mutation reported in ARX is an in-frame 24 bp duplication in exon 2, which causes an expansion of the polyalanine tract at amino acid positions 144–155, from 12 to 20 alanines. This duplication has been reported in a Norwegian family with West Syndrome [3,4] as well as four published nonsyndromic XLMR families, MRX36 [5], MRX43, MRX54 and MRX76 [6]. We have recently identified the same 24 bp duplication in 4 other nonsyndromic XLMR families linked to Xp22.1: MRX29 [7], MRX32 [8], MRX33 [9], and MRX38 [10]. "
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    ABSTRACT: X-linked mental retardation (XLMR) is the leading cause of mental retardation in males. Mutations in the ARX gene in Xp22.1 have been found in numerous families with both nonsyndromic and syndromic XLMR. The most frequent mutation in this gene is a 24 bp duplication in exon 2. Based on this fact, a panel of XLMR families linked to Xp22 was tested for this particular ARX mutation. Genomic DNA from XLMR families linked to Xp22.1 was amplified for exon 2 in ARX using a Cy5 labeled primer pair. The resulting amplicons were sized using the ALFexpress automated sequencer. A panel of 11 families with X-linked mental retardation was screened for the ARX 24dup mutation. Four nonsyndromic XLMR families - MRX29, MRX32, MRX33 and MRX38 - were found to have this particular gene mutation. We have identified 4 additional XLMR families with the ARX dup24 mutation from a panel of 11 XLMR families linked to Xp22.1. This finding makes the ARX dup24 mutation the most common mutation in nonsyndromic XLMR families linked to Xp22.1. As this mutation can be readily tested for using an automated sequencer, screening should be considered for any male with nonsyndromic MR of unknown etiology.
    BMC Medical Genetics 05/2005; 6(1):16. DOI:10.1186/1471-2350-6-16 · 2.08 Impact Factor
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    ABSTRACT: The aetiology of mental retardation (MR) was studied in a population-based series of Norwegian children derived from 30 037 children born between 1980 and 1985. The study included 178 children, 79 with severe MR (SMR) (IQ
    Developmental Medicine & Child Neurology 02/2000; 42(2). DOI:10.1111/j.1469-8749.2000.tb00050.x · 3.51 Impact Factor
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