X-linked congenital ptosis and associated intellectual disability, short stature, microcephaly, cleft palate, digital and genital abnormalities define novel Xq25q26 duplication syndrome

R. S. Moller, L. R. Jensen, S. M. Maas, J. Filmus, M. Capurro, C. Hansen, C. L. M. Marcelis, K. Ravn, J. Andrieux, M. Mathieu, M. Kirchhoff, O. K. Rodningen, N. de Leeuw, H. G. Yntema, G. Froyen, J. Vandewalle, K. Ballon, E. Klopocki, S. Joss, J. TolmieA. C. Knegt, A. M. Lund, H. Hjalgrim, A. W. Kuss, N. Tommerup, R. Ullmann, A. P. M. de Brouwer, P. Stromme, S. Kjaergaard, Z. Tumer, T. Kleefstra

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Submicroscopic duplications along the long arm of the X-chromosome with known phenotypic consequences are relatively rare events. The clinical features resulting from such duplications are various, though they often include intellectual disability, microcephaly, short stature, hypotonia, hypogonadism and feeding difficulties. Female carriers are often phenotypically normal or show a similar but milder phenotype, as in most cases the X-chromosome harbouring the duplication is subject to inactivation. Xq28, which includes MECP2 is the major locus for submicroscopic X-chromosome duplications, whereas duplications in Xq25 and Xq26 have been reported in only a few cases. Using genome-wide array platforms we identified overlapping interstitial Xq25q26 duplications ranging from 0.2 to 4.76 Mb in eight unrelated families with in total five affected males and seven affected females. All affected males shared a common phenotype with intrauterine- and postnatal growth retardation and feeding difficulties in childhood. Three had microcephaly and two out of five suffered from epilepsy. In addition, three males had a distinct facial appearance with congenital bilateral ptosis and large protruding ears and two of them showed a cleft palate. The affected females had various clinical symptoms similar to that of the males with congenital bilateral ptosis in three families as most remarkable feature. Comparison of the gene content of the individual duplications with the respective phenotypes suggested three critical regions with candidate genes (AIFM1, RAB33A, GPC3 and IGSF1) for the common phenotypes, including candidate loci for congenital bilateral ptosis, small head circumference, short stature, genital and digital defects.
OriginalsprogEngelsk
TidsskriftHuman Genetics
Vol/bind133
Udgave nummer5
Sider (fra-til)625-638
ISSN0340-6717
DOI
StatusUdgivet - 2014

Bibliografisk note

ISI Document Delivery No.: AF2CJ Times Cited: 1 Cited Reference Count: 36 Moller, R. S. Jensen, L. R. Maas, S. M. Filmus, J. Capurro, M. Hansen, C. Marcelis, C. L. M. Ravn, K. Andrieux, J. Mathieu, M. Kirchhoff, M. Rodningen, O. K. de Leeuw, N. Yntema, H. G. Froyen, G. Vandewalle, J. Ballon, K. Klopocki, E. Joss, S. Tolmie, J. Knegt, A. C. Lund, A. M. Hjalgrim, H. Kuss, A. W. Tommerup, N. Ullmann, R. de Brouwer, A. P. M. Stromme, P. Kjaergaard, S. Tuemer, Z. Kleefstra, T. Kleefstra, Tjitske/G-2619-2012 German Federal Ministry of Education and Research, NGFNplus [PNR-01GS08161] We gratefully acknowledge the patients for their invaluable contribution to this study. Wilhelm Johannsen Centre for Functional Genome Research is established by the Danish National Research Foundation. RU was supported by a grant from the German Federal Ministry of Education and Research, NGFNplus, Grant No. PNR-01GS08161. 1 SPRINGER NEW YORK HUM GENET

Emneord

  • APOPTOSIS-INDUCING FACTOR MENTAL-RETARDATION ARRAY-CGH FUNCTIONAL DISOMY MUTATIONS PHENOTYPE GROWTH GENES GIRL INACTIVATION

Citer dette

Moller, R. S. ; Jensen, L. R. ; Maas, S. M. ; Filmus, J. ; Capurro, M. ; Hansen, C. ; Marcelis, C. L. M. ; Ravn, K. ; Andrieux, J. ; Mathieu, M. ; Kirchhoff, M. ; Rodningen, O. K. ; de Leeuw, N. ; Yntema, H. G. ; Froyen, G. ; Vandewalle, J. ; Ballon, K. ; Klopocki, E. ; Joss, S. ; Tolmie, J. ; Knegt, A. C. ; Lund, A. M. ; Hjalgrim, H. ; Kuss, A. W. ; Tommerup, N. ; Ullmann, R. ; de Brouwer, A. P. M. ; Stromme, P. ; Kjaergaard, S. ; Tumer, Z. ; Kleefstra, T. / X-linked congenital ptosis and associated intellectual disability, short stature, microcephaly, cleft palate, digital and genital abnormalities define novel Xq25q26 duplication syndrome. I: Human Genetics. 2014 ; Bind 133, Nr. 5. s. 625-638.
@article{e9fe0e6ec2c34b76972115a62db18cd7,
title = "X-linked congenital ptosis and associated intellectual disability, short stature, microcephaly, cleft palate, digital and genital abnormalities define novel Xq25q26 duplication syndrome",
abstract = "Submicroscopic duplications along the long arm of the X-chromosome with known phenotypic consequences are relatively rare events. The clinical features resulting from such duplications are various, though they often include intellectual disability, microcephaly, short stature, hypotonia, hypogonadism and feeding difficulties. Female carriers are often phenotypically normal or show a similar but milder phenotype, as in most cases the X-chromosome harbouring the duplication is subject to inactivation. Xq28, which includes MECP2 is the major locus for submicroscopic X-chromosome duplications, whereas duplications in Xq25 and Xq26 have been reported in only a few cases. Using genome-wide array platforms we identified overlapping interstitial Xq25q26 duplications ranging from 0.2 to 4.76 Mb in eight unrelated families with in total five affected males and seven affected females. All affected males shared a common phenotype with intrauterine- and postnatal growth retardation and feeding difficulties in childhood. Three had microcephaly and two out of five suffered from epilepsy. In addition, three males had a distinct facial appearance with congenital bilateral ptosis and large protruding ears and two of them showed a cleft palate. The affected females had various clinical symptoms similar to that of the males with congenital bilateral ptosis in three families as most remarkable feature. Comparison of the gene content of the individual duplications with the respective phenotypes suggested three critical regions with candidate genes (AIFM1, RAB33A, GPC3 and IGSF1) for the common phenotypes, including candidate loci for congenital bilateral ptosis, small head circumference, short stature, genital and digital defects.",
keywords = "APOPTOSIS-INDUCING FACTOR MENTAL-RETARDATION ARRAY-CGH FUNCTIONAL DISOMY MUTATIONS PHENOTYPE GROWTH GENES GIRL INACTIVATION",
author = "Moller, {R. S.} and Jensen, {L. R.} and Maas, {S. M.} and J. Filmus and M. Capurro and C. Hansen and Marcelis, {C. L. M.} and K. Ravn and J. Andrieux and M. Mathieu and M. Kirchhoff and Rodningen, {O. K.} and {de Leeuw}, N. and Yntema, {H. G.} and G. Froyen and J. Vandewalle and K. Ballon and E. Klopocki and S. Joss and J. Tolmie and Knegt, {A. C.} and Lund, {A. M.} and H. Hjalgrim and Kuss, {A. W.} and N. Tommerup and R. Ullmann and {de Brouwer}, {A. P. M.} and P. Stromme and S. Kjaergaard and Z. Tumer and T. Kleefstra",
note = "ISI Document Delivery No.: AF2CJ Times Cited: 1 Cited Reference Count: 36 Moller, R. S. Jensen, L. R. Maas, S. M. Filmus, J. Capurro, M. Hansen, C. Marcelis, C. L. M. Ravn, K. Andrieux, J. Mathieu, M. Kirchhoff, M. Rodningen, O. K. de Leeuw, N. Yntema, H. G. Froyen, G. Vandewalle, J. Ballon, K. Klopocki, E. Joss, S. Tolmie, J. Knegt, A. C. Lund, A. M. Hjalgrim, H. Kuss, A. W. Tommerup, N. Ullmann, R. de Brouwer, A. P. M. Stromme, P. Kjaergaard, S. Tuemer, Z. Kleefstra, T. Kleefstra, Tjitske/G-2619-2012 German Federal Ministry of Education and Research, NGFNplus [PNR-01GS08161] We gratefully acknowledge the patients for their invaluable contribution to this study. Wilhelm Johannsen Centre for Functional Genome Research is established by the Danish National Research Foundation. RU was supported by a grant from the German Federal Ministry of Education and Research, NGFNplus, Grant No. PNR-01GS08161. 1 SPRINGER NEW YORK HUM GENET",
year = "2014",
doi = "10.1007/s00439-013-1403-3",
language = "English",
volume = "133",
pages = "625--638",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Heinemann",
number = "5",

}

Moller, RS, Jensen, LR, Maas, SM, Filmus, J, Capurro, M, Hansen, C, Marcelis, CLM, Ravn, K, Andrieux, J, Mathieu, M, Kirchhoff, M, Rodningen, OK, de Leeuw, N, Yntema, HG, Froyen, G, Vandewalle, J, Ballon, K, Klopocki, E, Joss, S, Tolmie, J, Knegt, AC, Lund, AM, Hjalgrim, H, Kuss, AW, Tommerup, N, Ullmann, R, de Brouwer, APM, Stromme, P, Kjaergaard, S, Tumer, Z & Kleefstra, T 2014, 'X-linked congenital ptosis and associated intellectual disability, short stature, microcephaly, cleft palate, digital and genital abnormalities define novel Xq25q26 duplication syndrome', Human Genetics, bind 133, nr. 5, s. 625-638. https://doi.org/10.1007/s00439-013-1403-3

X-linked congenital ptosis and associated intellectual disability, short stature, microcephaly, cleft palate, digital and genital abnormalities define novel Xq25q26 duplication syndrome. / Moller, R. S.; Jensen, L. R.; Maas, S. M.; Filmus, J.; Capurro, M.; Hansen, C.; Marcelis, C. L. M.; Ravn, K.; Andrieux, J.; Mathieu, M.; Kirchhoff, M.; Rodningen, O. K.; de Leeuw, N.; Yntema, H. G.; Froyen, G.; Vandewalle, J.; Ballon, K.; Klopocki, E.; Joss, S.; Tolmie, J.; Knegt, A. C.; Lund, A. M.; Hjalgrim, H.; Kuss, A. W.; Tommerup, N.; Ullmann, R.; de Brouwer, A. P. M.; Stromme, P.; Kjaergaard, S.; Tumer, Z.; Kleefstra, T.

I: Human Genetics, Bind 133, Nr. 5, 2014, s. 625-638.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - X-linked congenital ptosis and associated intellectual disability, short stature, microcephaly, cleft palate, digital and genital abnormalities define novel Xq25q26 duplication syndrome

AU - Moller, R. S.

AU - Jensen, L. R.

AU - Maas, S. M.

AU - Filmus, J.

AU - Capurro, M.

AU - Hansen, C.

AU - Marcelis, C. L. M.

AU - Ravn, K.

AU - Andrieux, J.

AU - Mathieu, M.

AU - Kirchhoff, M.

AU - Rodningen, O. K.

AU - de Leeuw, N.

AU - Yntema, H. G.

AU - Froyen, G.

AU - Vandewalle, J.

AU - Ballon, K.

AU - Klopocki, E.

AU - Joss, S.

AU - Tolmie, J.

AU - Knegt, A. C.

AU - Lund, A. M.

AU - Hjalgrim, H.

AU - Kuss, A. W.

AU - Tommerup, N.

AU - Ullmann, R.

AU - de Brouwer, A. P. M.

AU - Stromme, P.

AU - Kjaergaard, S.

AU - Tumer, Z.

AU - Kleefstra, T.

N1 - ISI Document Delivery No.: AF2CJ Times Cited: 1 Cited Reference Count: 36 Moller, R. S. Jensen, L. R. Maas, S. M. Filmus, J. Capurro, M. Hansen, C. Marcelis, C. L. M. Ravn, K. Andrieux, J. Mathieu, M. Kirchhoff, M. Rodningen, O. K. de Leeuw, N. Yntema, H. G. Froyen, G. Vandewalle, J. Ballon, K. Klopocki, E. Joss, S. Tolmie, J. Knegt, A. C. Lund, A. M. Hjalgrim, H. Kuss, A. W. Tommerup, N. Ullmann, R. de Brouwer, A. P. M. Stromme, P. Kjaergaard, S. Tuemer, Z. Kleefstra, T. Kleefstra, Tjitske/G-2619-2012 German Federal Ministry of Education and Research, NGFNplus [PNR-01GS08161] We gratefully acknowledge the patients for their invaluable contribution to this study. Wilhelm Johannsen Centre for Functional Genome Research is established by the Danish National Research Foundation. RU was supported by a grant from the German Federal Ministry of Education and Research, NGFNplus, Grant No. PNR-01GS08161. 1 SPRINGER NEW YORK HUM GENET

PY - 2014

Y1 - 2014

N2 - Submicroscopic duplications along the long arm of the X-chromosome with known phenotypic consequences are relatively rare events. The clinical features resulting from such duplications are various, though they often include intellectual disability, microcephaly, short stature, hypotonia, hypogonadism and feeding difficulties. Female carriers are often phenotypically normal or show a similar but milder phenotype, as in most cases the X-chromosome harbouring the duplication is subject to inactivation. Xq28, which includes MECP2 is the major locus for submicroscopic X-chromosome duplications, whereas duplications in Xq25 and Xq26 have been reported in only a few cases. Using genome-wide array platforms we identified overlapping interstitial Xq25q26 duplications ranging from 0.2 to 4.76 Mb in eight unrelated families with in total five affected males and seven affected females. All affected males shared a common phenotype with intrauterine- and postnatal growth retardation and feeding difficulties in childhood. Three had microcephaly and two out of five suffered from epilepsy. In addition, three males had a distinct facial appearance with congenital bilateral ptosis and large protruding ears and two of them showed a cleft palate. The affected females had various clinical symptoms similar to that of the males with congenital bilateral ptosis in three families as most remarkable feature. Comparison of the gene content of the individual duplications with the respective phenotypes suggested three critical regions with candidate genes (AIFM1, RAB33A, GPC3 and IGSF1) for the common phenotypes, including candidate loci for congenital bilateral ptosis, small head circumference, short stature, genital and digital defects.

AB - Submicroscopic duplications along the long arm of the X-chromosome with known phenotypic consequences are relatively rare events. The clinical features resulting from such duplications are various, though they often include intellectual disability, microcephaly, short stature, hypotonia, hypogonadism and feeding difficulties. Female carriers are often phenotypically normal or show a similar but milder phenotype, as in most cases the X-chromosome harbouring the duplication is subject to inactivation. Xq28, which includes MECP2 is the major locus for submicroscopic X-chromosome duplications, whereas duplications in Xq25 and Xq26 have been reported in only a few cases. Using genome-wide array platforms we identified overlapping interstitial Xq25q26 duplications ranging from 0.2 to 4.76 Mb in eight unrelated families with in total five affected males and seven affected females. All affected males shared a common phenotype with intrauterine- and postnatal growth retardation and feeding difficulties in childhood. Three had microcephaly and two out of five suffered from epilepsy. In addition, three males had a distinct facial appearance with congenital bilateral ptosis and large protruding ears and two of them showed a cleft palate. The affected females had various clinical symptoms similar to that of the males with congenital bilateral ptosis in three families as most remarkable feature. Comparison of the gene content of the individual duplications with the respective phenotypes suggested three critical regions with candidate genes (AIFM1, RAB33A, GPC3 and IGSF1) for the common phenotypes, including candidate loci for congenital bilateral ptosis, small head circumference, short stature, genital and digital defects.

KW - APOPTOSIS-INDUCING FACTOR MENTAL-RETARDATION ARRAY-CGH FUNCTIONAL DISOMY MUTATIONS PHENOTYPE GROWTH GENES GIRL INACTIVATION

U2 - 10.1007/s00439-013-1403-3

DO - 10.1007/s00439-013-1403-3

M3 - Journal article

C2 - 24326587

VL - 133

SP - 625

EP - 638

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 5

ER -