Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium.

Arjan P.M. de Brouwer, Helger G. Yntema, Tjitske Kleefstra, Dorien Lugtenberg, Astrid R. Oudakker, Bert B.A. de Vries, Hans van Bokhoven, Hilde Van Esch, Suzanne G.M. Frints, Guy Froyen, Jean Pierre Fryns, Martine Raynaud, Marie Pierre Moizard, Nathalie Ronce, Anissa Bensalem, Claude Moraine, Karine Poirier, Laetitia Castelnau, Yoann Saillour, Thierry Bienvenu & 13 others Chérif Beldjord, Vincent des Portes, Jamel Chelly, Gillian Turner, Tod Fullston, Jozef Gecz, Andreas W. Kuss, Andreas Tzschach, Lars Riff Jensen, Steffen Lenzner, Vera M. Kalscheuer, Hans Hilger Ropers, Ben C.J. Hamel

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Abstract

The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes. For 42% of the families with obligate female carriers, the mental retardation phenotype could be explained by a mutation. There was no difference between families with (lod score >2) or without (lod score <2) significant linkage to the X chromosome. For families with two to five affected brothers (brother pair=BP families) only 17% of the MR could be explained. This is significantly lower (P=0.0067) than in families with obligate carrier females and indicates that the MR in about 40% (17/42) of the BP families is due to a single genetic defect on the X chromosome. The mutation frequency of XLMR genes in BP families is lower than can be expected on basis of the male to female ratio of patients with MR or observed recurrence risks. This might be explained by genetic risk factors on the X chromosome, resulting in a more complex etiology in a substantial portion of XLMR patients. The EuroMRX effort is the first attempt to unravel the molecular basis of cognitive dysfunction by large-scale approaches in a large patient cohort. Our results show that it is now possible to identify 42% of the genetic defects in non-syndromic and syndromic XLMR families with obligate female carriers. (c) 2006 Wiley-Liss, Inc.

LanguageEnglish
Pages207-208
Number of pages2
JournalHuman Mutation
Volume28
Issue number2
DOIs
Publication statusPublished - 1 Jan 2007

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

de Brouwer, A. P. M., Yntema, H. G., Kleefstra, T., Lugtenberg, D., Oudakker, A. R., de Vries, B. B. A., ... Hamel, B. C. J. (2007). Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium. Human Mutation, 28(2), 207-208. https://doi.org/10.1002/humu.9482
de Brouwer, Arjan P.M. ; Yntema, Helger G. ; Kleefstra, Tjitske ; Lugtenberg, Dorien ; Oudakker, Astrid R. ; de Vries, Bert B.A. ; van Bokhoven, Hans ; Van Esch, Hilde ; Frints, Suzanne G.M. ; Froyen, Guy ; Fryns, Jean Pierre ; Raynaud, Martine ; Moizard, Marie Pierre ; Ronce, Nathalie ; Bensalem, Anissa ; Moraine, Claude ; Poirier, Karine ; Castelnau, Laetitia ; Saillour, Yoann ; Bienvenu, Thierry ; Beldjord, Chérif ; des Portes, Vincent ; Chelly, Jamel ; Turner, Gillian ; Fullston, Tod ; Gecz, Jozef ; Kuss, Andreas W. ; Tzschach, Andreas ; Jensen, Lars Riff ; Lenzner, Steffen ; Kalscheuer, Vera M. ; Ropers, Hans Hilger ; Hamel, Ben C.J. / Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium. In: Human Mutation. 2007 ; Vol. 28, No. 2. pp. 207-208.
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abstract = "The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes. For 42{\%} of the families with obligate female carriers, the mental retardation phenotype could be explained by a mutation. There was no difference between families with (lod score >2) or without (lod score <2) significant linkage to the X chromosome. For families with two to five affected brothers (brother pair=BP families) only 17{\%} of the MR could be explained. This is significantly lower (P=0.0067) than in families with obligate carrier females and indicates that the MR in about 40{\%} (17/42) of the BP families is due to a single genetic defect on the X chromosome. The mutation frequency of XLMR genes in BP families is lower than can be expected on basis of the male to female ratio of patients with MR or observed recurrence risks. This might be explained by genetic risk factors on the X chromosome, resulting in a more complex etiology in a substantial portion of XLMR patients. The EuroMRX effort is the first attempt to unravel the molecular basis of cognitive dysfunction by large-scale approaches in a large patient cohort. Our results show that it is now possible to identify 42{\%} of the genetic defects in non-syndromic and syndromic XLMR families with obligate female carriers. (c) 2006 Wiley-Liss, Inc.",
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de Brouwer, APM, Yntema, HG, Kleefstra, T, Lugtenberg, D, Oudakker, AR, de Vries, BBA, van Bokhoven, H, Van Esch, H, Frints, SGM, Froyen, G, Fryns, JP, Raynaud, M, Moizard, MP, Ronce, N, Bensalem, A, Moraine, C, Poirier, K, Castelnau, L, Saillour, Y, Bienvenu, T, Beldjord, C, des Portes, V, Chelly, J, Turner, G, Fullston, T, Gecz, J, Kuss, AW, Tzschach, A, Jensen, LR, Lenzner, S, Kalscheuer, VM, Ropers, HH & Hamel, BCJ 2007, 'Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium.', Human Mutation, vol. 28, no. 2, pp. 207-208. https://doi.org/10.1002/humu.9482

Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium. / de Brouwer, Arjan P.M.; Yntema, Helger G.; Kleefstra, Tjitske; Lugtenberg, Dorien; Oudakker, Astrid R.; de Vries, Bert B.A.; van Bokhoven, Hans; Van Esch, Hilde; Frints, Suzanne G.M.; Froyen, Guy; Fryns, Jean Pierre; Raynaud, Martine; Moizard, Marie Pierre; Ronce, Nathalie; Bensalem, Anissa; Moraine, Claude; Poirier, Karine; Castelnau, Laetitia; Saillour, Yoann; Bienvenu, Thierry; Beldjord, Chérif; des Portes, Vincent; Chelly, Jamel; Turner, Gillian; Fullston, Tod; Gecz, Jozef; Kuss, Andreas W.; Tzschach, Andreas; Jensen, Lars Riff; Lenzner, Steffen; Kalscheuer, Vera M.; Ropers, Hans Hilger; Hamel, Ben C.J.

In: Human Mutation, Vol. 28, No. 2, 01.01.2007, p. 207-208.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium.

AU - de Brouwer, Arjan P.M.

AU - Yntema, Helger G.

AU - Kleefstra, Tjitske

AU - Lugtenberg, Dorien

AU - Oudakker, Astrid R.

AU - de Vries, Bert B.A.

AU - van Bokhoven, Hans

AU - Van Esch, Hilde

AU - Frints, Suzanne G.M.

AU - Froyen, Guy

AU - Fryns, Jean Pierre

AU - Raynaud, Martine

AU - Moizard, Marie Pierre

AU - Ronce, Nathalie

AU - Bensalem, Anissa

AU - Moraine, Claude

AU - Poirier, Karine

AU - Castelnau, Laetitia

AU - Saillour, Yoann

AU - Bienvenu, Thierry

AU - Beldjord, Chérif

AU - des Portes, Vincent

AU - Chelly, Jamel

AU - Turner, Gillian

AU - Fullston, Tod

AU - Gecz, Jozef

AU - Kuss, Andreas W.

AU - Tzschach, Andreas

AU - Jensen, Lars Riff

AU - Lenzner, Steffen

AU - Kalscheuer, Vera M.

AU - Ropers, Hans Hilger

AU - Hamel, Ben C.J.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes. For 42% of the families with obligate female carriers, the mental retardation phenotype could be explained by a mutation. There was no difference between families with (lod score >2) or without (lod score <2) significant linkage to the X chromosome. For families with two to five affected brothers (brother pair=BP families) only 17% of the MR could be explained. This is significantly lower (P=0.0067) than in families with obligate carrier females and indicates that the MR in about 40% (17/42) of the BP families is due to a single genetic defect on the X chromosome. The mutation frequency of XLMR genes in BP families is lower than can be expected on basis of the male to female ratio of patients with MR or observed recurrence risks. This might be explained by genetic risk factors on the X chromosome, resulting in a more complex etiology in a substantial portion of XLMR patients. The EuroMRX effort is the first attempt to unravel the molecular basis of cognitive dysfunction by large-scale approaches in a large patient cohort. Our results show that it is now possible to identify 42% of the genetic defects in non-syndromic and syndromic XLMR families with obligate female carriers. (c) 2006 Wiley-Liss, Inc.

AB - The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes. For 42% of the families with obligate female carriers, the mental retardation phenotype could be explained by a mutation. There was no difference between families with (lod score >2) or without (lod score <2) significant linkage to the X chromosome. For families with two to five affected brothers (brother pair=BP families) only 17% of the MR could be explained. This is significantly lower (P=0.0067) than in families with obligate carrier females and indicates that the MR in about 40% (17/42) of the BP families is due to a single genetic defect on the X chromosome. The mutation frequency of XLMR genes in BP families is lower than can be expected on basis of the male to female ratio of patients with MR or observed recurrence risks. This might be explained by genetic risk factors on the X chromosome, resulting in a more complex etiology in a substantial portion of XLMR patients. The EuroMRX effort is the first attempt to unravel the molecular basis of cognitive dysfunction by large-scale approaches in a large patient cohort. Our results show that it is now possible to identify 42% of the genetic defects in non-syndromic and syndromic XLMR families with obligate female carriers. (c) 2006 Wiley-Liss, Inc.

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de Brouwer APM, Yntema HG, Kleefstra T, Lugtenberg D, Oudakker AR, de Vries BBA et al. Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium. Human Mutation. 2007 Jan 1;28(2):207-208. https://doi.org/10.1002/humu.9482