Abstract
We investigated a family with a duplication, dup(X)q26-q27, that was present in two brothers, their mother, and their maternal grandmother. The brothers carrying the duplication displayed spina bifida and panhypopituitarism, whereas a third healthy brother inherited the normal X chromosome. Preferential inactivation of the X chromosome containing the duplication was evident in healthy carrierd females. We determined the boundaries of the Xq26-q27 duplication. Via interphase FISH analysis we natrowed down each of the two breakpoint regions to ~300-kb intervals. The proximal breakpoint is located in Xq26.1 between DXS1114 and HPRT and is conrained in YAC yWXD599, while the distal breakpoint is located in Xq27.3 between DXS369 and DXS1200 and contained in YAC yWXD758. The duplication comprises about 13 Mb. Evidence from the literature points to a predisposing gene for spina bifida in Xq27. We hypothesize that the spina bifida in the two brothers may be due to interruption of a critical gene in the Xq27 breakpoint region. Several candidate genes were mapped to the Xq27 critical region but none was shown to be disrupted by the duplication event. Recently, M. Lagerstrom-Fermer et al. (1997, Am. J. Hum. Genet. 60, 910-916) reported on a family with X-linked recessive panhypopituitarism associated with a duplication in Xq26; however, no details were reported on the extent of the duplication. Our study corroborates their hypothesis that X-linked recessive panhypopituitarism is likely to be caused by a gene encoding a dosage-sensitive protein involved in pituitary development. We place the putative gene between DXS1114 and DXS1200, corresponding to the interval defined by the duplication in the present family. (C) 2000 Academic Press.
| Original language | English |
|---|---|
| Pages (from-to) | 174-181 |
| Number of pages | 8 |
| Journal | Genomics |
| Volume | 69 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Oct 15 2000 |
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- Genetics
Cite this
Identification and characterization of an Xq26-q27 duplication in a family with spina bifida and panhypopituitarism suggests the involvement of two distinct genes. / Hol, Frans A.; Schepens, Marga T.; Van Beersum, S. E C; Redolfi, Elena; Affer, Maurizio; Vezzoni, Paolo; Hamel, B. C J; Karnes, Pamela S.; Mariman, E. C M; Zucchi, Ileana.
In: Genomics, Vol. 69, No. 2, 15.10.2000, p. 174-181.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Identification and characterization of an Xq26-q27 duplication in a family with spina bifida and panhypopituitarism suggests the involvement of two distinct genes
AU - Hol, Frans A.
AU - Schepens, Marga T.
AU - Van Beersum, S. E C
AU - Redolfi, Elena
AU - Affer, Maurizio
AU - Vezzoni, Paolo
AU - Hamel, B. C J
AU - Karnes, Pamela S.
AU - Mariman, E. C M
AU - Zucchi, Ileana
PY - 2000/10/15
Y1 - 2000/10/15
N2 - We investigated a family with a duplication, dup(X)q26-q27, that was present in two brothers, their mother, and their maternal grandmother. The brothers carrying the duplication displayed spina bifida and panhypopituitarism, whereas a third healthy brother inherited the normal X chromosome. Preferential inactivation of the X chromosome containing the duplication was evident in healthy carrierd females. We determined the boundaries of the Xq26-q27 duplication. Via interphase FISH analysis we natrowed down each of the two breakpoint regions to ~300-kb intervals. The proximal breakpoint is located in Xq26.1 between DXS1114 and HPRT and is conrained in YAC yWXD599, while the distal breakpoint is located in Xq27.3 between DXS369 and DXS1200 and contained in YAC yWXD758. The duplication comprises about 13 Mb. Evidence from the literature points to a predisposing gene for spina bifida in Xq27. We hypothesize that the spina bifida in the two brothers may be due to interruption of a critical gene in the Xq27 breakpoint region. Several candidate genes were mapped to the Xq27 critical region but none was shown to be disrupted by the duplication event. Recently, M. Lagerstrom-Fermer et al. (1997, Am. J. Hum. Genet. 60, 910-916) reported on a family with X-linked recessive panhypopituitarism associated with a duplication in Xq26; however, no details were reported on the extent of the duplication. Our study corroborates their hypothesis that X-linked recessive panhypopituitarism is likely to be caused by a gene encoding a dosage-sensitive protein involved in pituitary development. We place the putative gene between DXS1114 and DXS1200, corresponding to the interval defined by the duplication in the present family. (C) 2000 Academic Press.
AB - We investigated a family with a duplication, dup(X)q26-q27, that was present in two brothers, their mother, and their maternal grandmother. The brothers carrying the duplication displayed spina bifida and panhypopituitarism, whereas a third healthy brother inherited the normal X chromosome. Preferential inactivation of the X chromosome containing the duplication was evident in healthy carrierd females. We determined the boundaries of the Xq26-q27 duplication. Via interphase FISH analysis we natrowed down each of the two breakpoint regions to ~300-kb intervals. The proximal breakpoint is located in Xq26.1 between DXS1114 and HPRT and is conrained in YAC yWXD599, while the distal breakpoint is located in Xq27.3 between DXS369 and DXS1200 and contained in YAC yWXD758. The duplication comprises about 13 Mb. Evidence from the literature points to a predisposing gene for spina bifida in Xq27. We hypothesize that the spina bifida in the two brothers may be due to interruption of a critical gene in the Xq27 breakpoint region. Several candidate genes were mapped to the Xq27 critical region but none was shown to be disrupted by the duplication event. Recently, M. Lagerstrom-Fermer et al. (1997, Am. J. Hum. Genet. 60, 910-916) reported on a family with X-linked recessive panhypopituitarism associated with a duplication in Xq26; however, no details were reported on the extent of the duplication. Our study corroborates their hypothesis that X-linked recessive panhypopituitarism is likely to be caused by a gene encoding a dosage-sensitive protein involved in pituitary development. We place the putative gene between DXS1114 and DXS1200, corresponding to the interval defined by the duplication in the present family. (C) 2000 Academic Press.
UR - http://www.scopus.com/inward/record.url?scp=0034667325&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034667325&partnerID=8YFLogxK
U2 - 10.1006/geno.2000.6327
DO - 10.1006/geno.2000.6327
M3 - Article
C2 - 11031100
AN - SCOPUS:0034667325
VL - 69
SP - 174
EP - 181
JO - Genomics
JF - Genomics
SN - 0888-7543
IS - 2
ER -