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Partial Xp duplication in a girl with dysmorphic features: the change in replication pattern of late‐replicating dupX chromosome
Author(s) -
Kokalj Vokac N,
Seme Ciglenecki P,
Erjavec A,
Zagradisnik B,
Zagorac A
Publication year - 2002
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.2002.610111.x
Subject(s) - biology , genetics , gene duplication , yeast artificial chromosome , x inactivation , x chromosome , chromosome , microbiology and biotechnology , gene , gene mapping
In this paper we present the case of a girl at the age of 32 months with dysmorphic features, including general muscular hypotonia, developmental delay and mental retardation. The cytogenetic analysis revealed de novo partial duplication of Xp: 46,X,dup(X)(p11.23→p22.33: :p11.23→p22.33). To characterize the duplication, X painting, Kallman (KAL), yeast artificial chromosomes (YACs) and bacterial artificial chromosomes (BACs) covering Xp11.23→Xp22.33 region were used. Selective inactivation of the abnormal X chromosome using Hpa II digestion of the AR gene was evident. After BrdU incorporation the abnormal X was late‐replicating in all lymphocytes examined. There was one peculiar exception observed: the break‐point region was consistently early replicating. The replicating pattern of this region corresponded to the active X chromosome. Methylation pattern of late replicating X chromosome was studied also using antibodies against 5‐methylcytosine. The pattern corresponded to the normally inactive X chromosome, with the exception of the previously observed break‐point region which revealed an early replicating pattern with strong fluorescent signal, similar to the pattern of the active X chromosome. The observed phenomenon could lead to the abnormal phenotype of the patient, with some normally inactive genes of the break‐point region escaping the inactivation process. The abnormal clinical findings could also be due to tissue‐dependent differences in the inactivation pattern.