Characterisation of an inverted X chromosome (p11.2q21.3) associated with mental retardation using FISH.

Abstract

We report on a patient with a pericentric inversion of the X chromosome, 46,Y,inv(X)(p11.2q21.3), who was referred for cytogenetic analysis because of mild mental retardation, short stature, prepubescent macro-orchidism, and submucous cleft palate. The same chromosomal abnormality was found in the proband's mother. The inverted X chromosome was late replicating in all the mother's lymphocytes studied, indicative of a likely unbalanced inversion. We show, by fluorescence in situ hybridisation (FISH) using a panel of ordered yeast artificial chromosome (YAC) clones, that the Xp breakpoint is localised in Xpl 1.23 between DXS146 and DXS255 and that the Xq breakpoint is assigned to the X-Y homologous region in Xq21.3. YACs crossing the Xp and Xq breakpoints have been identified. One of these two breakpoints could be linked to the mental retardation in this patient as many non-specific mental retardation (MRX) loci have previously been located in the pericentromeric region of the X chromosome. Morever, the elucidation at the molecular level of this rearrangement will also indicate if cleft palate or prepubescent macro-orchidism, or both, in this boy are related to one of the two X breakpoints. (7Med Genet 1998;35:146-150)

Inv(X)(p21.1;q22.1) in a man with mental retardation, short stature, general muscle wasting, and facial dysmorphism: Clinical study and mutation analysis of the NXF5 Gene

“…All reported patients were women with short stature, secondary amenorrhoea or oligomenorrhea, and premature ovarian failure [Maraschio et al, 1996], except one male fetus (spontaneous abortion) without fetal pathological data [Allderdice and Eales, 1981]. A single report of a man with a pericentric inversion Xp11.2-Xq21.3, partial GHD, and MR fits with an interrupted gene in the breakpoint region of Xq21.3 [Sloan-Bena et al, 1998]. In this region, men with small cytogenetically visible duplications have also been described [Shapira et al, 1997].…”

Detection of pericentric inversion of X chromosome in a male fetus

“…Fragile X molecular studies were negative. DNA replication studies on maternal peripheral blood showed skewed X inactivation of the inverted X, suggesting an unbalanced inversion [Sloan-Bena et al, 1998]. In a study of a three-generation family, the inv(X)(p21.1q26) cosegregated with Duchenne muscular dystrophy, suggesting disruption of the gene at the Xp21.1 breakpoint.…”

A pericentric inversion of chromosome X disruptingF8and resulting in haemophilia A

“…Heterozygotes with a X chromosome pericentric inversion may have four possible X gametic types [X, inv(X), dup(p)/del(q) and dup(q)/del(p)], and may cause abnormal offspring or recurrent abortions. Males with gene deletions or duplications in the Xq13→q21.3 region or even extending to Xq24 region may have mental retardation, short stature, growth retardation, hypogonadism and general muscle hypotonia 23 24…”