Recurrent Deletions and Reciprocal Duplications of 10q11.21q11.23 Including CHAT and SLC18A3 are Likely Mediated by Complex Low-Copy Repeats

被引：39

作者：

Stankiewicz, Pawel ^{[1
,2
]}

Kulkarni, Shashikant ^{[3
,4
,5
,6
]}

Dharmadhikari, Avinash V. ^{[1
]}

Sampath, Srirangan ^{[1
]}

Bhatt, Samarth S. ^{[1
]}

Shaikh, Tamim H. ^{[7
]}

Xia, Zhilian ^{[1
]}

Pursley, Amber N. ^{[1
]}

Cooper, M. Lance ^{[1
]}

Shinawi, Marwan ^{[4
]}

Paciorkowski, Alex R. ^{[9
]}

Grange, Dorothy K. ^{[4
]}

Noetzel, Michael J. ^{[8
]}

Saunders, Scott ^{[10
]}

Simons, Paul ^{[10
]}

Summar, Marshall ^{[11
]}

Lee, Brendan ^{[1
]}

Scaglia, Fernando ^{[1
]}

Fellmann, Florence ^{[12
]}

Martinet, Danielle ^{[12
]}

Beckmann, Jacques S. ^{[12
,13
]}

Asamoah, Alexander ^{[14
]}

Platky, Kathryn ^{[14
]}

Sparks, Susan ^{[15
]}

Martin, Ann S. ^{[15
]}

Madan-Khetarpal, Suneeta ^{[16
]}

Hoover, Jacqueline ^{[16
]}

Medne, Livija ^{[17
]}

Bonnemann, Carsten G. ^{[17
]}

Moeschler, John B. ^{[18
]}

Vallee, Stephanie E. ^{[18
]}

Parikh, Sumit ^{[19
]}

Irwin, Polly ^{[19
]}

Dalzell, Victoria P. ^{[20
]}

Smith, Wendy E. ^{[20
]}

Banks, Valerie C. ^{[20
]}

Flannery, David B. ^{[21
]}

Lovell, Carolyn M. ^{[21
]}

Bellus, Gary A. ^{[7
]}

Golden-Grant, Kathryn ^{[7
]}

Gorski, Jerome L. ^{[22
]}

Kussmann, Jennifer L. ^{[22
]}

McGregor, Tracy L. ^{[23
,24
]}

Hamid, Rizwan ^{[23
,24
]}

Pfotenhauer, Jean ^{[23
,24
]}

Ballif, Blake C. ^{[25
]}

Shaw, Chad A. ^{[1
]}

Kang, Sung-Hae L. ^{[1
]}

Bacino, Carlos A. ^{[1
]}

Patel, Ankita ^{[1
]}

机构：

[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[2] Inst Mother & Child Hlth, Dept Med Genet, Warsaw, Poland

[3] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA

[4] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[6] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA

[7] Univ Colorado Denver, Dept Pediat, Aurora, CO USA

[8] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA

[9] Seattle Childrens Res Inst, Seattle, WA USA

[10] Washington Univ, Sch Med, Dept Pediat Newborn Med, St Louis, MO USA

[11] Childrens Natl Med Ctr, Washington, DC USA

[12] CHU Vaudois, Serv Genet Med, Lausanne, Switzerland

[13] Univ Lausanne, Dept Med Genet, CH-1015 Lausanne, Switzerland

[14] Univ Louisville, Dept Pediat, Weisskopf Child Evaluat Ctr, Louisville, KY 40292 USA

[15] Carolinas Med Ctr, Charlotte, NC 28203 USA

[16] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA

[17] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA

[18] Dartmouth Hitchcock Med Ctr, Childrens Hosp Dartmouth, Lebanon, NH 03766 USA

[19] Cleveland Clin, Ctr Pediat Neurol, Cleveland, OH 44106 USA

[20] Maine Med Partners, Portland, ME USA

[21] Georgia Hlth Sci Univ, Dept Pediat, Med Coll Georgia, Augusta, GA USA

[22] Univ Missouri, Div Med Genet, Columbia, MO USA

[23] Vanderbilt Univ, Dept Pediat, Sch Med, Nashville, TN USA

[24] Monroe Carell Jr Childrens Hosp Vanderbilt, Nashville, TN USA

[25] PerkinElmer Inc, Signature Genom Labs, Spokane, WA USA

来源：

HUMAN MUTATION | 2012年 / 33卷 / 01期

关键词：

CHAT; SLC18A3; genomic rearrangement; array CGH; UNRECOGNIZED MICRODELETION SYNDROME; COMPARATIVE GENOMIC HYBRIDIZATION; INTERSTITIAL DELETION; MENTAL-RETARDATION; LONG ARM; SEGMENTAL DUPLICATIONS; DEVELOPMENTAL DELAY; COCKAYNE-SYNDROME; DNA-SEQUENCE; REARRANGEMENTS;

D O I：

10.1002/humu.21614

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplications have additional copy number changes. Detailed clinical evaluation of 20 patients with deletions revealed variable clinical features, with developmental delay (DD) and/or intellectual disability (ID) as the only features common to a majority of individuals. We suggest that some of the other features present in more than one patient with deletion, including hypotonia, sleep apnea, chronic constipation, gastroesophageal and vesi-coureteral refluxes, epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping in the first intron of CHAT and encoding vesicular acetylcholine transporter. The phenotypic diversity and presence of the deletion in apparently normal carrier parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit variable phenotypic expressivity and incomplete penetrance influenced by additional genetic and nongenetic modifiers. Hum Mutat 33:165-179, 2012. (C) 2011 Wiley Periodicals, Inc.

引用

页码：165 / 179

页数：15

共 3 条

[1] 22q11.21 Deletions: A Review on the Interval Mediated by Low-Copy Repeats C and D
Bertini, Veronica
Cambi, Francesca
Legitimo, Annalisa
Costagliola, Giorgio
Consolini, Rita
Valetto, Angelo
GENES, 2025, 16 (01)
[2] Recurrent 10q11.2 deletions unmasking CHAT or SLC18A3 recessive mutations can lead to congenital myasthenic syndrome
Whalen, S.
Schwartz, M.
Benzarti, A.
Afenjar, A.
Isapof, A.
Chabrol, B.
Portnoi, M.
Nicole, S.
Sternberg, D.
Heide, S.
Chantot-Bastaraud, S.
Siffroi, J.
EUROPEAN JOURNAL OF HUMAN GENETICS, 2018, 26 : 623 - 624
[3] How chromosomal deletions can unmask recessive mutations? Deletions in 10q11.2 associated with CHAT or SLC18A3 mutations lead to congenital myasthenic syndrome
Schwartz, Mathias
Sternberg, Damien
Whalen, Sandra
Afenjar, Alexandra
Isapof, Arnaud
Chabrol, Brigitte
Portnoi, Marie-France
Heide, Solveig
Keren, Boris
Chantot-Bastaraud, Sandra
Siffroi, Jean-Pierre
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2018, 176 (01) : 151 - 155

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