We report on two brothers and one maternal cousin with severe mental retardation, microcephaly, short stature, cryptorchidism, and spastic diplegia. The patients were born to normal and non-consanguineous parents. All other members of the family, almost exclusively females, were clinically normal, suggesting X linked inheritance. By multipoint linkage analysis with markers spanning the whole X chromosome, we have tentatively assigned the underlying genetic defect to Xp11.4-q21, achieving a maximum lod score of 1.3. This localisation overlaps MRXS3, a syndromic form of mental retardation resembling that found in the family described here, although with a milder presentation. We discuss the possibility that both phenotypes might be allelic variants of the same gene localised in the pericentromeric region of the X chromosome. Analysis of the X inactivation pattern in one potential and three obligate carrier females showed non-random inactivation of the allele linked to the disease. This finding may be interpreted as: (1) a negative selection effect on cells bearing the mutation on the active X chromosome; (2) both the disease causing gene and the X inactivation centre are simultaneously affected by the same alteration, a deletion for instance; or (3) the skewed inactivation is the consequence of an independent event randomly associated with the disease. In any case, the observation of consistent X inactivation supports X linkage of the disease.
%0 Journal Article
%1 Martinez1998a
%A Mart?nez, F.
%A Tom?s, M.
%A Mill?n, J. M.
%A Fern?ndez, A.
%A Palau, F.
%A Prieto, F.
%D 1998
%J J Med Genet
%K Abnormalities, Multiple; Adolescent; Centromere; Cerebral Palsy; Child; Chromosome Mapping; Dosage Compensation, Genetic; Female; Heterozygote; Humans; Linkage (Genetics); Male; Mental Retardation; Pedigree; X
%N 4
%P 284--287
%T Genetic localisation of mental retardation with spastic diplegia to the pericentromeric region of the X chromosome: X inactivation in female carriers.
%V 35
%X We report on two brothers and one maternal cousin with severe mental retardation, microcephaly, short stature, cryptorchidism, and spastic diplegia. The patients were born to normal and non-consanguineous parents. All other members of the family, almost exclusively females, were clinically normal, suggesting X linked inheritance. By multipoint linkage analysis with markers spanning the whole X chromosome, we have tentatively assigned the underlying genetic defect to Xp11.4-q21, achieving a maximum lod score of 1.3. This localisation overlaps MRXS3, a syndromic form of mental retardation resembling that found in the family described here, although with a milder presentation. We discuss the possibility that both phenotypes might be allelic variants of the same gene localised in the pericentromeric region of the X chromosome. Analysis of the X inactivation pattern in one potential and three obligate carrier females showed non-random inactivation of the allele linked to the disease. This finding may be interpreted as: (1) a negative selection effect on cells bearing the mutation on the active X chromosome; (2) both the disease causing gene and the X inactivation centre are simultaneously affected by the same alteration, a deletion for instance; or (3) the skewed inactivation is the consequence of an independent event randomly associated with the disease. In any case, the observation of consistent X inactivation supports X linkage of the disease.
@article{Martinez1998a,
abstract = {We report on two brothers and one maternal cousin with severe mental retardation, microcephaly, short stature, cryptorchidism, and spastic diplegia. The patients were born to normal and non-consanguineous parents. All other members of the family, almost exclusively females, were clinically normal, suggesting X linked inheritance. By multipoint linkage analysis with markers spanning the whole X chromosome, we have tentatively assigned the underlying genetic defect to Xp11.4-q21, achieving a maximum lod score of 1.3. This localisation overlaps MRXS3, a syndromic form of mental retardation resembling that found in the family described here, although with a milder presentation. We discuss the possibility that both phenotypes might be allelic variants of the same gene localised in the pericentromeric region of the X chromosome. Analysis of the X inactivation pattern in one potential and three obligate carrier females showed non-random inactivation of the allele linked to the disease. This finding may be interpreted as: (1) a negative selection effect on cells bearing the mutation on the active X chromosome; (2) both the disease causing gene and the X inactivation centre are simultaneously affected by the same alteration, a deletion for instance; or (3) the skewed inactivation is the consequence of an independent event randomly associated with the disease. In any case, the observation of consistent X inactivation supports X linkage of the disease.},
added-at = {2014-07-19T20:45:47.000+0200},
author = {Mart?nez, F. and Tom?s, M. and Mill?n, J. M. and Fern?ndez, A. and Palau, F. and Prieto, F.},
biburl = {https://www.bibsonomy.org/bibtex/21520db11f85322c5c08492645b28152f/ar0berts},
groups = {public},
interhash = {d116a9aa757679f441bba5f7d8c1d184},
intrahash = {1520db11f85322c5c08492645b28152f},
journal = {J Med Genet},
keywords = {Abnormalities, Multiple; Adolescent; Centromere; Cerebral Palsy; Child; Chromosome Mapping; Dosage Compensation, Genetic; Female; Heterozygote; Humans; Linkage (Genetics); Male; Mental Retardation; Pedigree; X},
month = Apr,
number = 4,
pages = {284--287},
pmid = {9598720},
timestamp = {2014-07-19T20:45:47.000+0200},
title = {Genetic localisation of mental retardation with spastic diplegia to the pericentromeric region of the X chromosome: X inactivation in female carriers.},
username = {ar0berts},
volume = 35,
year = 1998
}