X;14 translocation: An exception to the critical region hypothesis on the human X‐chromosome

Abstract

We report on a family in which an X;14 translocation has been identified. A phenotypically normal female, carrier of an apparently balanced X-autosome translocation t(X;14)(q22;q24.3) in all her cells and a small interstitial deletion of band 15q112 in some of her cells had 2 offspring. She represents a fifth case of balanced X-autosome translocation with the break point inside the postulated critical region of Xq(q13 q26) associated with fertility. The break point in this case is located in Xq22, the same band as in four previously published exceptional cases. In most of her cells, the normal X was inactivated. Her daughter, the proposita, has an unbalanced karyotype 46,X,der(X), t(X;14)(q22;q24.3)mat, del(15)(q11.1q11.3)mat. She is mildly retarded and has some Prader-Willi syndrome manifestations. She has two normal 14 chromosomes, der(X), and deletion 15q11.2. Her clinical abnormalities probably could be attributed to the deletions 15q and Xq rather than 14q duplication. In most of cells, der(X) was inactivated. We assume that spreading of inactivation was extended to the 14q segment on the derivative X. Late replication and gene dose studies support this view. Another daughter, who inherited the balanced X;14 translocation and not deletion 15 chromosome, is phenotypically normal.

Functional disomies of the X chromosome influence the cell selection and hence the X inactivation pattern in females with balanced X‐autosome translocations: A review of 122 cases

“…The evidence for such a disomy is presented in our case report in this issue [Du Sart et al, 19911. This case seems to be representative of all balanced translocations with inactivation of Xt, as the cytogenetic data are quite consistent in all of them, i.e., either der(X) or der(A) is late replicating, and never both (e.g., Zabel et al, 1978;Hellkuhl et al, 1982;Kajii et al, 1985;Markovic et al, 1985;Journel et al, 1990). Among the 28 translocations with the reported inactivation of Xt, der(X) was late replicating in 25 (90%) and der(A) in 3 (10%).…”

Whole‐arm t (X;17) (Xp17q;Xq17p) and gonadal dysgenesis

“…According to the critical region hypothesis (Sarto et al 1973, Summitt et al 1978, female carriers of X;Autosome (X;A) translocations have gonadal dysfunction or dysgenesis and are infertile if the X-breakpoint is located within the critical segment Xq13+q26; otherwise, ovarian function is preserved (Mattei et al 1982, Madan 1983. Nevertheless, at least five female carriers of X;A translocations with the X-breakpoint within the critical segment and proven fertility are exceptions to such a hypothesis (Cann et al 1975, Barnabei et al 1981, Madan et al 1981, Wegner 1982, Markovic et al 1985. We report here a further, though opposite, exception: a young woman with gonadal dysgenesis and a whole-arm X; 17 translocation.…”