{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T22:56:25Z","timestamp":1780354585347,"version":"3.54.1"},"reference-count":19,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,4]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1136\/jmg.35.4.284","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"284-287","source":"Crossref","is-referenced-by-count":15,"title":["Genetic localisation of mental retardation with spastic diplegia to the pericentromeric region of the X chromosome: X inactivation in female carriers."],"prefix":"10.1136","volume":"35","author":[{"given":"F","family":"Mart\u00ednez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Tom\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Mill\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Palau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Prieto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1998,4,1]]},"reference":[{"key":"ref_1","first-page":"147","article-title":"XLMR genes: update","volume":"64","author":"Lubs, H.A.; Chiurazzi, P.; Arena, J.F.; Schwartz, C.; Tranebjaerg, L.; Neri, G.","year":"1996","unstructured":"Lubs HA, Chiurazzi P, Arena JF, Schwartz C, Tranebjaerg L, Neri G. 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