вход по аккаунту


Complex chromosomal translocation in a patient with Kallmann syndrome

код для вставкиСкачать
American Journal of Medical Genetics 91:240 (2000)
Letter to the Editor
Complex Chromosomal Translocation in a Patient
With Kallmann Syndrome
To the Editor:
Kallmann syndrome is characterized by a hypogonadotrophic hypogonadism and anosmia in affected
male patients. A gene (KALX) for Kallmann syndrome
(KS) was mapped to the short arm of the X chromosome
at band Xp22.3 [Franco et al., 1991]. Mutations of that
gene or microdeletions of this chromosomal segment
account for probably all X-linked cases of KS. However,
there is good evidence that at least one autosomal gene
exists, which when mutated gives rise to an autosomal
dominant form of KS [Merriam et al., 1977]. The existence of an autosomal recessive form of KS was also
suggested, although a dominant gene with reduced
penetrance has to be considered in such families [Hardelin et al., 1993]. Three cases with chromosomal rearrangements were reported so far, where the patients
had the characteristic phenotype of KS, with few or no
additional clinical findings [Best et al., 1990; Casamassima et al., 1993; Schinzel et al., 1995].
The propositus described here was initially suspected of having Aarskog syndrome because of his hypogenitalism, with a shawl scrotum, small testes, and a
micropenis. Minor anomalies like a broad nasal bridge
and a long philtrum were noted. He underwent repeated cycles of hormonal treatment and orchidopexis.
At the age of 4 years a biopsy of his testes indicated a
severely reduced number of spermatogonia (about 1/10)
per testicular canaliculi. At the age of 16 years, following hormonal stimulation by the GnRH test, an increase of LH and FSH but not of testosterone was recorded. At 17 years the patient, who was otherwise
normal with regard to physical and psychomotor development, was subjected to further investigations because of his anosmia and the hypogonadotrophic hypogonadism. Brain MRI indicated no abnormalities of the
pituitary gland; however, the bilateral absence of the
bulbus olfactorius and the anterior sulcus olfactorius
allowed the diagnosis of KS.
Cytogenetic analysis showed a complex chromosomal
rearrangement (CCR) involving chromosomes 3, 13,
and 18. By high-resolution banding and FISH with
whole chromosome painting probes it was possible to
*Correspondence to: Dr. Peter Michael Kroisel, University of
Graz, Institute of Medical Biology and Human Genetics, Harrachgasse 21/8, A-8010 Graz, Austria.
Received 11 May 1999; Accepted 13 December 1999
© 2000 Wiley-Liss, Inc.
demonstrate that in addition to the translocation
t(3;13;18), a paracentric inversion of the long arm of
chromosome 3 was also present, resulting in the following karyotype: 46,XY,inv(3)(q24q26.32),t(3;13;18)
(q26.32;q21.2;q12.2). Application of a commercially
available FISH probe (LSI Kallmann’s Region Probe,
Vysis) ruled out a detectable microdeletion of the KALX
gene. The mother’s chromosomes were normal. The father was not available for analysis, but he is reportedly
a normal man. This patient represents the fourth reported case with an autosomal form of KS combined
with a chromosomal anomaly. It is intriguing that all
reported cases have different chromosomal breakpoints, although in the present case as well as in the
patient reported by Casamassima et al. [1993] the long
arm of chromosome 3 is involved, although with a different breakpoint. We have established a lymphoblastoid cell line of the patient and further molecular studies might allow identification of an autosomal gene
locus for a dominant form of KS.
Best LG, Wasdahl WA, Larson LM, Sturlaugson J. 1990. Chromosome
abnormality in Kallmann syndrome. Am J Med Genet 35:306–309.
Casamassima AC, Wilmot PL, Vibert BK, Shapiro LR. 1993. Kallmann
syndrome associated with complex chromosome rearrangement. Am J
Med Genet 45:539–541.
Franco B, Guioli S, Pragliola A, Incerti B, Bardoni B, Tonlorenzi R, Carrozzo R, Maestrini E, Pieretti M, Taillon-Miller P, Brown CJ, Willard
HF, Lawrence C, Persio MG, Camerino G, 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 JP, Levilliers J, Blanchard S, Carel JC, Leutenegger M, PinardBertelletto JP, Bouloux P, Petit C. 1993. Heterogeneity in the mutations responsible for X-chromosome-linked Kallmann syndrome. Hum
Mol Genet 2:373–377.
Merriam GR, Beitins IZ, Bode HH. 1977. Father-to-son transmission of
hypogonadism with anosmia, Kallmann’s syndrome. Am J Dis Child
Schinzel A, Lorda-Sanchez I, Binkert F, Carter NP, Bebb CE, FergusonSmith MA, Eiholzer U, Zachmann M, Robinson WP. 1995. Kallmann
syndrome in a boy with a t(1;10) translocation detected by reverse
chromosome painting. J Med Genet 32:957–961.
Peter M. Kroisel*
Erwin Petek
Klaus Wagner
Institute of Medical Biology and Human Genetics
University of Graz
Graz, Austria
Peter Kurnik
Department of Pediatrics
Klagenfurt Hospital
Klagenfurt, Austria
Без категории
Размер файла
45 Кб
complex, patients, kallmann, syndrome, chromosome, translocation
Пожаловаться на содержимое документа