X-linked non specific mental retardation (MRX) accounts for ~ 25% of mental retardation in males. Despite this high frequency, little is known about the molecular defects underlying this disorder, mainly because of the clinical and genetic heterogeneity, which is evident from linkage studies. A wide variety of MRX loci have been mapped on X chromosome. At least 8 MRX genes have been identified, but each accounts for only 0.5-1.0% of MRX cases. Here we report two MRX families. The first family has nine males in two generations with classic X-linked inheritance of variable degree of non specific mental retardation. We have performed on this family a two point linkage analysis that shows tight linkage for marker GATA72E05 with Lod Score of 3.14 at ?=0.00. Two point linkage interval corresponds to roughly 23 cM in the pericentromeric region of X chromosome. According to linkage data and their functional characteristic, we are performing the mutational screening of some genes in this region to prove their involvement in this pathology. The second family is composed by eight males in three generation characterised by a mild to severe X-linked mental retardation. Previous analysis linked this family in Xq28 between marker DXS1073 and F8c (Lod Score=2.71 at ?=0.00). We have performed mutational analysis for 10 candidate genes present in this region by sequencing and RT-PCR analysis and we have found some known and unknown polymorphisms. We are now looking for other candidate genes and we are performing further analysis to exclude genomic rearrangements.
Genetic analysis of two unrelated Italian Families with non specific X-mental retardation.
Miano MG;Ciccodicola A;
2002
Abstract
X-linked non specific mental retardation (MRX) accounts for ~ 25% of mental retardation in males. Despite this high frequency, little is known about the molecular defects underlying this disorder, mainly because of the clinical and genetic heterogeneity, which is evident from linkage studies. A wide variety of MRX loci have been mapped on X chromosome. At least 8 MRX genes have been identified, but each accounts for only 0.5-1.0% of MRX cases. Here we report two MRX families. The first family has nine males in two generations with classic X-linked inheritance of variable degree of non specific mental retardation. We have performed on this family a two point linkage analysis that shows tight linkage for marker GATA72E05 with Lod Score of 3.14 at ?=0.00. Two point linkage interval corresponds to roughly 23 cM in the pericentromeric region of X chromosome. According to linkage data and their functional characteristic, we are performing the mutational screening of some genes in this region to prove their involvement in this pathology. The second family is composed by eight males in three generation characterised by a mild to severe X-linked mental retardation. Previous analysis linked this family in Xq28 between marker DXS1073 and F8c (Lod Score=2.71 at ?=0.00). We have performed mutational analysis for 10 candidate genes present in this region by sequencing and RT-PCR analysis and we have found some known and unknown polymorphisms. We are now looking for other candidate genes and we are performing further analysis to exclude genomic rearrangements.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.