The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

被引：97

作者：

Koolen, David A. ^{[1
,2
]}

Pfundt, Rolph ^{[1
,2
]}

Linda, Katrin ^{[1
,2
]}

Beunders, Gea ^{[3
]}

Veenstra-Knol, Hermine E. ^{[4
]}

Conta, Jessie H. ^{[5
]}

Fortuna, Ana Maria ^{[6
]}

Gillessen-Kaesbach, Gabriele ^{[7
]}

Dugan, Sarah ^{[8
]}

Halbach, Sara ^{[9
]}

Abdul-Rahman, Omar A. ^{[10
]}

Winesett, Heather M. ^{[11
]}

Chung, Wendy K. ^{[12
]}

Dalton, Marguerite ^{[13
]}

Dimova, Petia S. ^{[14
]}

Mattina, Teresa ^{[15
]}

Prescott, Katrina ^{[16
]}

Zhang, Hui Z. ^{[17
]}

Saal, Howard M. ^{[18
]}

Hehir-Kwa, Jayne Y. ^{[1
,2
]}

Willemsen, Marjolein H. ^{[1
,2
]}

Ockeloen, Charlotte W. ^{[1
,2
]}

Jongmans, Marjolijn C. ^{[1
,2
]}

Van der Aa, Nathalie ^{[19
]}

Failla, Pinella ^{[20
]}

Barone, Concetta ^{[20
]}

Avola, Emanuela ^{[20
]}

Brooks, Alice S. ^{[21
]}

Kant, Sarina G. ^{[22
]}

Gerkes, Erica H. ^{[4
]}

Firth, Helen V. ^{[23
]}

Ounap, Katrin ^{[24
]}

Bird, Lynne M. ^{[25
,26
,27
,28
]}

Masser-Frye, Diane ^{[25
,26
,27
,28
]}

Friedman, Jennifer R. ^{[25
,26
,27
,28
]}

Sokunbi, Modupe A. ^{[29
]}

Dixit, Abhijit ^{[30
]}

Splitt, Miranda ^{[31
]}

Kukolich, Mary K. ^{[32
]}

McGaughran, Julie ^{[33
,34
]}

Coe, Bradley P. ^{[35
]}

Florez, Jesus ^{[36
]}

Kasri, Nael Nadif ^{[1
,2
]}

Brunner, Han G. ^{[1
,2
,37
]}

Thompson, Elizabeth M. ^{[38
,39
]}

Gecz, Jozef ^{[40
,41
]}

Romano, Corrado ^{[20
]}

Eichler, Evan E. ^{[35
,42
]}

de Vries, Bert B. A. ^{[1
,2
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Human Genet, Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands

[3] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

[4] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[5] Seattle Childrens Hosp, Dept Labs, Seattle, WA USA

[6] Ctr Hosp Porto, Ctr Genet Med Dr Jacinto Magalhaes, Unidade Genet Med, Oporto, Portugal

[7] Med Univ Lubeck, Inst Humangenet, D-23538 Lubeck, Germany

[8] Childrens Hosp & Clin Minnesota, Dept Genet, Minneapolis, MN USA

[9] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[10] Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA

[11] St Lukes Pediat Associates, Duluth, MN USA

[12] Columbia Univ, Dept Pediat & Med, New York, NY USA

[13] Counties Manukau Dist Hlth Board, South Auckland, New Zealand

[14] St Ivan Rilski Univ Hosp, Epilepsy Ctr, Sofia, Bulgaria

[15] Univ Catania, Dept Pediat, Med Genet, Catania, Italy

[16] Yorkshire Reg Genet Serv, Clin Genet, Leeds, W Yorkshire, England

[17] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA

[18] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA

[19] Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium

[20] IRCCS Assoc Oasi Maria Santissima, Pediat & Med Genet, Troina, Italy

[21] Erasmus MC, Sophia Childrens Hosp, Dept Clin Genet, Rotterdam, Netherlands

[22] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands

[23] Univ Cambridge, Addenbrookes Hosp, Dept Med Genet, Cambridge CB2 2QQ, England

[24] Tartu Univ Hosp, United Labs, Dept Genet, Tartu, Estonia

[25] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA

[26] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA

[27] Rady Childrens Hosp San Diego, Div Neurol, San Diego, CA USA

[28] Rady Childrens Hosp San Diego, Div Genet, San Diego, CA USA

[29] Nacogdoches Pediat, Nacogdoches, TX USA

[30] City Hosp Nottingham, Clin Genet, Nottingham, England

[31] Inst Med Genet, Northern Genet Serv, Newcastle Upon Tyne, Tyne & Wear, England

[32] Cook Childrens Hosp, Clin Genet, Ft Worth, TX USA

[33] Royal Brisbane & Womens Hosp, Genet Hlth Queensland, Brisbane, Qld, Australia

[34] Univ Queensland, Sch Med, Brisbane, Qld, Australia

[35] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA

[36] Univ Cantabria, Dept Physiol & Pharmacol, Cantabria, Spain

[37] Maastricht Univ, Med Ctr, Dept Clin Genet, NL-6200 MD Maastricht, Netherlands

[38] Womens & Childrens Hosp, South Australian Clin Genet Serv, Adelaide, SA, Australia

[39] Univ Adelaide, Dept Paediat, Adelaide, SA, Australia

[40] Univ Adelaide, Womens & Childrens Hosp, Sch Paediat & Reprod Hlth, Adelaide, SA, Australia

[41] Univ Adelaide, Womens & Childrens Hosp, Robinson Res Inst, Adelaide, SA, Australia

[42] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2016年 / 24卷 / 05期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

COMMON INVERSION; COMPLEX; MAPT; DELINEATION; MUTATIONS; GENE;

D O I：

10.1038/ejhg.2015.178

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.

引用

页码：652 / 659

页数：8

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