Full text in pdf format

Clinical and molecular studies in a mother and son with Xp22.3 deletion

Diana Ternes Pereira^I; José Carlos Cabral de Almeida^II; Michael Patton^III; Steve Jeffery^III

^IDepartamento de Clínica Médica, Hospital Universitário, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brasil. Send correspondence to E.T.P.
^IICentro de Genética Médica, IFF, FIOCRUZ, Rio de Janeiro, Brasil. Unidade de Citogenética Humana, IBCCFo., Universidade Federal do Rio de Janeiro, Brasil
^IIISouth West Thames Regional Genetics Unit, St. George's Hospital Medical School, Crammer Terrace, London SW17 ORE, England

ABSTRACT

We studied a young man presenting short stature, moderate mental retardation, seizures, ichthyosis, anosmia and hypogonadotrophic hypogonadism (Kallmann's syndrome). The cytogenetic analysis identified a maternally inherited X-Y translocation (Xp22.3;Yq11). The results of the molecular studies were compatible with contiguous gene syndrome. The presence of decreased carpal arch in the mother and deformities of the medial tibial condyle in both the propositus and his mother associates these abnormalities with the loss of a segment of the X chromosome.

Keywords: clinical; molecular; mother; son; Xp22.3 deletion.

REFERENCES

Agematsu, K., Koike, K., Morosawa, H., Nakahori, Y., Nakagome, Y. and Akabane, T. (1988). Chondrodysplasia punctata with X;Y translocation. Hum. Genet. 80: 105-107.

Akesson, H.O., Hagberg, B. and Wahlström, J. (1980). Y-to-X chromosome translocation observed in two generations. Hum. Genet. 55: 39-42.

Ballabio, A., Parenti, G., Tippet, P., Mondello, C., Di Maio, S., Tenore, A. and Andria, G. (1986). X-linked ichthyosis, due to steroid sulphatase deficiency, associated with Kalimann syndrome (hypogonadotropic hypogonadism and anosmia): linkage relationships with Xg and cloned DNA sequences from the distal short arm of the X chromosome. Hum. Genet. 72: 237-240.

Ballabio, A., Parenti, G., Carozzo, R., Coppa, G., Feilci, L., Migliori, V., Silengo, M., Franceschini, P. and Andria, G. (1988). X/Y translocation in a family with X-linked ichthyosis, chondrodysplasia punctata and mental retardation: DNA analysis reveals deletion of the steroid sulfatase gene and translocation of its pseudogene. Clin. Genet. 34: 31-37.

Ballabio, A., Bardoni, B., Carrozo, R., Andria, G., Bick, D., Campbell, L., Hamel, B., Ferguson-Smith, M.A., Gimelli, G., Fraccaro, M., Maraschio, P., Zuffardi, O., Guioli, S. and Camerino, G. (1989). Contiguous gene syndromes due to deletions in the distal short arm of the human X chromosome. Proc. Natl. Acad. Sci. USA 86: 10001-10005.

Bonifas, J.M., Morey, B.J., Oakey, R.E., Kan, Y.W. and Epstein, E.H. (1987). Cloning of a cDNA for steroid sulfatase: frequent occurrence of gene deletions in patients with recessive X chromosome-linked ichthyosis. Proc. Natl. Acad. Sci. USA 84: 9248-9251.

Curry, C.J.R., Lanmam, J.T., Magenis, R.E., Brown, M.G., Bergner, E.A. and Shapiro, L.J. (1982). X-linked chondrodysplasia punctata with ichthyosis: chromosomal localization to Xp. Am. J. Hum. Genet. 34: 122A.

Curry, C.J.R., Magenis, R., Brown, M., Lanman, J.T., Tsai, J., O'Lague, P., Goodfellow, P., Mohandas, T., Bergener, A. and Shapiro, L.J. (1984). Inherited chondrodysplasia punctata due to a deletion of the terminal short arm of an X chromosome. N. Engl. J. Med. 311: 1010-1015.

Franco, B., Guioli, S., Pragliola, A., Incerti, B., Bardoni, B., Tonlorenzi, R., Carrozzo, R., Maestrini, E., Pieretti, M., Taillon-Miller, P., Brown, C.J., Willard, H.F., Lawrence, C., Persico, M.G., Camerino, G. and Ballabio, A. (1991). A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature 353: 529-536.

Hardelin, J.-P., Levilliers, J., Young, J., Pholsena, M., Legouis, R., Kirk, J., Bouloux, P., Petit, C. and Schaison, G. (1993). Xp22.3 deletions in isolated familial Kallmann's syndrome. J. Clin. Endocrinol. Metab. 76: 827-831.

Hsu, T.-Y., Gibson, L.H., Yen, P.H., Pober, B.R. and Yang-Feng, T.L. (1994). FISH analysis of a subtle familial Xp deletion in a female patient with Madelung deformity. Am. J. Hum. Genet. 55: A107.

Khudr, G., Benirschke, K., Judd, H.L. and Strauss, J. (1973). Y to X translocation in a woman with reproductive failure. JAMA 226: 544-549.

Kosowicz, J. (1962). The carpal sign in gonadal dysgenesis. J: Clin. Endocrinol. Metab. 22: 949-952.

Kosowicz, J. and Poland, P. (1960). The deformity of the medial tibial condyle in nineteen cases of gonadal dysgenesis. J. Bone Joint. Surg. 42-A: 600-604.

Kunkel, L.M., Smith, K.D., Boyer, S.H., Borgaonkar, D.S., Wachter, S.S., Miller, O.J., Breg, W.A., Jones, H.W. and Rory, J.M. (1977). Analysis of human Y-specific reiterated DNA in in chromosome variants. Proc. Nat. Acad. Sci. USA 74: 1245-1249.

Legouis, R., Hardelini, J.-P., Levilliers, J., Claverie, J.-M., Compain, S., Wunderie, V., Millasseau, P., Le Paslier, D., Cohen, D., Caterina, D., Bougheleret, L., Van de Waal, H.D., Lutfala, G., Weissenbach, J. and Petit, C. (1991). The candidate gene for the X-linked Kalimann syndrome encodes a protein related to adhesion molecules. Cell 67: 423-435.

Matsumoto, T., Taku, K., Miike, T., Harada, N. and Niikawa, N. (1991). XY translocation in a boy with ichthyosis, hypogonadism, short stature and mental retardation. Clin. Genet. 39: 156-158.

Meitinger, T., Heye, B., Petit, C., Levilliers, J., Golla, A., Moraine, C., Dalla Piccola, B., Sipell, W.G., Murken, J. and Ballabio, A. (1990). Definitive localization of X-linked Kallmann syndrome (hypogonadrotropic hygoponadism and anosmia) to Xp22.3: close linkage to the hypervariable repeat sequence CRI-5232. Am. J. Hum. Genet. 47: 664-669.

Pereira, E.T., Cabral de Almeida, J.C., Cunha, A., Patton, M., Taylor, R. and Jeffery, S. (1991). Use of probes for ZFY, SRY, and the Y pseudoautosomal boundary in XX males, XX true hermaphrodites, and an XY female. J. Med. Genet. 28: 591-595.

Pfeiffer, R.A. (1980). Observations in a case of an X-Y translocation, t(X;Y)(p22;q11), in a mother and son. Cytogenet. Cell Genet. 26: 150-157.

Shapiro, L.J., Yen, P., Pomerantz, D., Martins, E., Rolewic, L. and Mohandas, T. (1989). Molecular studies of deletions at the human steroid sulfatase locus. Proc. Natl. Acad. Sci. USA 86: 8477-8481.

Simpson, J.L. (1975). Gonadal dysgenesis and abnormalities of the human sex chromosomes: current status of phenotypic-karyotypic correlations. Birth Defects S. XI, 4: 23-57.

Southern, E. (1975). Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98: 503-517.

Tiepolo, L., Zuffardi, O. and Rodewald, A. (1977). Nullisomy for the distal portion of Xp in a male child with a X/Y translocation. Hum. Genet. 39: 277-281.

Tiepolo, L., Zuffardi, O., Fraccaro, M., di Natale, D., Gargantini, L., Müller, C.R. and Ropers, H.H. (1980). Assignment by deletion mapping of the steroid sulfatase X-linked ichthyosis locus to Xp22.3. Hum. Genet. 54: 205-206.

van den Berghe, H., Petit, P. and Fryns, J.P. (1977). Y to X translocation in man. Hum. Genet. 36: 129-141.

Van Maldergem, L., Espeel, M., Roels, F., Petit, C., Dacremont, G., Wanders, R.J.A., Verloes, A. and Gillerot, Y. (1991). X-linked recessive chondrodysplasia punctata with XY translocation in a stillborn fetus. Hum. Genet. 87: 661-664.

Yen, P.H., Allen, E., Marsh, B., Mohandas, T. and Shapiro, L.J. (1986). Molecular cloning of a cDNA for steroid sulfatase. Am. J. Hum. Genet. 39: A227.

Zuffardi, O., Maraschio, P., Lo Curto, F., Muller, U., Giarola, A. and Perotti, L. (1982). The role of Yp in sex determination: new evidence from X/Y translocation. A. J. Med. Genet. 12: 175-184.