DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

Pregnancies known to be at increased risk for the 7q11.23 duplication. Prenatal testing using genomic testing that will detect the 7q11.23 duplication found in the proband may be offered when:

• A parent has the recurrent microduplication.
• The parents do not have the 7q11.23 duplication but have had a child with the 7q11.23 duplication syndrome. In this instance, the recurrence risk associated with the possibility of parental germline mosaicism or other predisposing genetic mechanisms is probably <1%.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although most centers would consider decisions about prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

Pregnancies not known to be at increased risk for the 7q11.23 duplication. CMA performed in a pregnancy not known to be at increased risk may detect the recurrent 7q11.23 microduplication.

Note: Whether a pregnancy is known or not known to be at increased risk for the 7q11.23 duplication , prenatal test results cannot reliably predict the phenotype.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the 7q11.23 duplication has been identified.

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Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

• Childhood Apraxia of Speech Association of North America (CASANA)

www.apraxia-kids.org

• Duplication Cares

Phone: 440-853-7023

Fax: 425-642-2514

Email: info@DuplicationCares.org

www.duplicationcares.org

• Unique: The Rare Chromosome Disorder Support Group

G1 The Stables

Station Road West

Oxted Surrey RH8 9EE

United Kingdom

Phone: +44 (0) 1883 723356

Email: info@rarechromo.org; rarechromo@aol.com

www.rarechromo.org

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Hat is Molecular Genetics??

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

7q11.23 Duplication Syndrome: Genes and Databases

Critical Region	Gene	Chromosome Locus	Protein
WBSCR	Not applicable	7q11​.23	Not applicable

Data are compiled from the following standard references: gene from HGNC; chromosome locus, locus name, critical region, complementation group from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B.

OMIM Entries for 7q11.23 Duplication Syndrome (View All in OMIM)

609757

WILLIAMS-BEUREN REGION DUPLICATION SYNDROME

Molecular Genetic Pathogenesis

Duplication mechanism. Both the duplication of the Williams-Beuren syndrome critical region (WBSCR) that causes the 7q11.23 duplication syndrome and the deletion of the WBSCR that causes Williams syndrome are mediated by the genomic structure of the region. The WBSCR is flanked by low copy repeats (LCRs) with high nucleotide sequence similarity that predisposes the region to nonallelic homologous recombination.

An inversion polymorphism at 7q11.23 in one parent has been detected in 20% of children with a classic de novo7q11.23 duplication [Morris et al 2015]. In approximately 25% of individuals with a classic Williams syndrome deletion, the unaffected parent in whom the chromosome deletion originated has the inversion [Osborne et al 2001, Bayés et al 2003, Hobart et al 2010]. Approximately 6% of the general population also has this inversion polymorphism [Hobart et al 2010], which does not cause clinical symptoms [Tam et al 2008]. Presence of the inversion polymorphism confers an increased risk for both 7q11.23 duplication and deletion, likely through increased difficulty in meiotic pairing between chromosomes with the 7q11.23 region in opposite orientations [Osborne et al 2001].

Genes of interest in this region. A number of genes have been mapped within the 7q11.23 duplication region:

• ELN encoding the structural protein elastin, a major component of elastic fibers found in many tissues [Debelle & Tamburro 1999]. Duplication of ELN is likely related to the increased risk for aortic dilation in 7q11.23duplication syndrome [Zarate et al 2014, Morris et al 2015, Parrott et al 2015]. Deletion of ELN is responsible for supravalvar aortic stenosis in Williams syndrome [Ewart et al 1993]. ELN pathogenic variants typically result inautosomal dominant SVAS [Li et al 1997], and also have been reported in congenital cutis laxa [Tassabehji et al 1998, Zhang et al 1999].
• GTF2I encoding general transcription factor IIi (GTF2I) (OMIM) [Pérez Jurado et al 1998], acts as an inducible multifunctional transcription factor in the nucleus [Roy 2012] and a regulator of agonist-induced calcium entry in the cytoplasm [Caraveo et al 2006]. Duplication of the gene is associated with separation anxiety [Mervis et al 2012]. Deletion mapping of families with supravalvar aortic stenosis plus (SVAS plus) has suggested that deletionof this gene has a negative effect on IQ [Morris et al 2003]. GTF2I haplotypes have been associated with severity of manifestations in autism spectrum disorders [Malenfant et al 2012], with low social anxiety and reduced social communication abilities in the general population [Crespi & Hurd 2014], and with influencing the relation between trait anxiety and brain response to aversive social cues [Jabbi et al 2015].

The relation of the remaining genes within the duplicated region to the 7q11.23 duplication phenotype is unknown. Note that in the list below genes marked with an * lie entirely within the low copy repeat (LCR) regions of 7q11.23.

• ABHD11 (encoding abhydrolase domain-containing protein 11) [Merla et al 2002]
• ABHD11-AS1 (encoding ABHD11 antisense RNA 1, tail-to-tail) (OMIM) [Brochier et al 2008]. This long non-coding RNA (lncRNA) has been shown to be neuroprotective in a mouse model of Huntington disease [Francelle et al 2015].
• BAZ1B (encoding bromodomain adjacent to zinc finger domain 1B) (OMIM) [Meng et al 1998, Peoples et al 1998]. The BAZ1B protein is part of the WICH chromatin remodeling complex [Bozhenok et al 2002].
• BCL7B (encoding B-cell CLL/lymphoma 7B) (OMIM) [Jadayel et al 1998, Meng et al 1998]. The BCL7B protein is a subunit of mammalian SWI/SNF tumor supressor complexes [Kadoch et al 2013].
• CLDN3 (encoding claudin 3) (OMIM) and CLDN4 (encoding claudin 4) (OMIM) [Paperna et al 1998]
• CLIP2 (encoding CAP-GLY domain-containing linker protein 2) (OMIM) [Hoogenraad et al 2004]. A recent study of two healthy adult sibs with heterozygous deletion of only CLIP2 suggested that copy number variants for this gene do not result in a clinical or psychological phenotype [Vandeweyer et al 2012]. The CLIP2 protein product is highly expressed in the nervous system and regulates the growth of membrane microtubules [Akhmanova et al 2001].
• DNAJC30 (encoding DnaJ homolog, subfamily C, member 30) [Merla et al 2002]. DNAJC30 is an uncharacterized member of the DNAJ molecular chaperone homology domain-containing protein family [Merla et al 2002].
• EIF4H (encoding eukaryotic translation initiation factor 4H) (OMIM) [Osborne et al 1996, Richter-Cook et al 1998]. eIF4H is a regulatory subunit within the protein translation initiation complex. It regulates the eIF4I RNAhelicase [Jackson et al 2010].
• FZD9 (encoding homolog of Drosophila frizzled 9) (OMIM) [Wang et al 1997]. FZD9 is a transmembrane cell surface receptor that binds to Wnt proteins to alter the beta catenin pathway [Karasawa et al 2002].
• GTF2IRD1 (encoding GTF2I repeat domain containing 1, WBSCR11, BEN, MUSTRD1) (OMIM) [O’Mahoney et al 1998, Franke et al 1999, Osborne et al 1999, Tassabehji et al 1998]. GTF2IRD1 is a member of the TFII-I transcription factor family [Tipney et al 2004]. GTF2IRD1 deletion has been implicated in the craniofacial features of Williams syndrome [Tassabehji et al 2005].
• * GTF2IRD2 (encoding GTF2I repeat domain containing 2) [Makeyev et al 2004, Tipney et al 2004]. Sometimes duplicated in Dup7. GTF2IRD2 is a member of the TFII-I transcription factor family [Tipney et al 2004].
• LAT2 (encoding linker for activation of T cells, family member 2; NTAL) (OMIM) [Doyle et al 2000, Martindale et al 2000]. LAT2 is a transmembrane adaptor protein controlling mast cell activation and survival [Roget et al 2008].
• LIMK1 (encoding lim kinase 1) (OMIM). LIMK1 protein is involved in remodeling of the cytoskeleton in neurons through regulation of actin polymerization and is thought to be important for neuronal plasticity [Arber et al 1998]. Deletion of LIMK1 has been implicated in the abnormality of visuospatial constructive cognition in Williams syndrome [Frangiskakis et al1996, Morris et al 2003, Hoogenraad et al 2004].
• MIR590 (encoding microRNA 590) (OMIM), an uncharacterized mircoRNA that was identified in a screen for human microRNAs that promoted neonatal cardiomyocyte proliferation [Eulalio et al 2012]
• MIR4284 (encoding microRNA 4284), an uncharacterized mircoRNA
• MLXIPL (encoding MLX-interacting protein-like) (OMIM) [Meng et al 1998, Cairo et al 2001], which is involved in lipid and glucose metabolism in the liver and in adipose tissue [Iizuka 2013]
• * NCF1 (encoding neutrophil cytosolic factor 1) [Chanock et al 2000]. Sometimes duplicated in Dup7. NCF1 is the cytosolic subunit of the NADPH oxidase complex [Volpp et al 1989].
• * NSUN5 (encoding NOP2/SUN domain family member 5) (OMIM) [Doll & Grzeschik 2001, Merla et al 2002], a ribosomal RNA methyltransferase that has been linked to stress response and life span in model organisms [Schosserer et al 2015]
• RFC2 (encoding replication factor C, subunit 2) (OMIM) [Peoples et al 1996, Osborne et al 1996], a subunit of the RFC complex which is required for DNA replication [Tsurimoto & Stillman 1989]
• STX1A (encoding syntaxin 1A) (OMIM) [Osborne et al 1997], a key component in neurotransmitter release and insulin secretion [Gerber & Südhof 2002]
• TBL2 (encoding transducin-beta-like 2 (OMIM) [Meng et al 1998, Pérez Jurado et al 1999]. Located in the endoplasmic reticulumm, the TBL2 protein is involved in the cellular stress response [Tsukumo et al 2014].
• * TRIM50 (encoding tripartate motif-containing protein 50) (OMIM) [Meng et al 1998], an E3 ubiquitin ligase [Micale et al 2008]
• VPS37D (encoding homolog of yeast vacuolar protein sorting 37) (OMIM) [Micale et al 2008]
• WBSCR22 (encoding Williams-Beuren chromosome region 22; MERM1) (OMIM) [Doll & Grzeschik 2001]. WBSCR22 contains a methyltransferase domain and is involved in ribosome biogenesis [Õunap et al 2013].
• WBSCR27 (encoding Williams-Beuren chromosome region 27) (OMIM) [Micale et al 2008]
• WBSCR28 (encoding Williams-Beuren chromosome region 28) (OMIM) [Micale et al 2008]

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References

Literature Cited

1.                      Akhmanova A, Hoogenraad CC, Drabek K, Stepanova T, Dortland B, Verkerk T, Vermeulen W, Burgering BM, De Zeeuw CI, Grosveld F, Galjart N. Clasps are CLIP-115 and -170 associating proteins involved in the regional regulation of microtubule dynamics in motile fibroblasts. Cell. 2001;104:923–35. [PubMed]

2.                      Arber S, Barbayannis FA, Hanser H, Schneider C, Stanyon CA, Bernard O, Caroni P. Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature. 1998;393:805–9. [PubMed]

3.                      Bakker E, Van Broeckhoven C, Bonten EJ, van de Vooren MJ, Veenema H, Van Hul W, Van Ommen GJ, Vandenberghe A, Pearson PL. Germline mosaicism and Duchenne muscular dystrophy mutations. Nature.1987;329:554–6. [PubMed]

4.                      Bayés M, Magano LF, Rivera N, Flores R, Pérez Jurado LA. Mutational mechanisms of Williams-Beuren syndrome deletions. Am J Hum Genet. 2003;73:131–51. [PMC free article] [PubMed]

5.                      Berg JS, Brunetti-Pierri N, Peters SU, Kang S-HL, Fong CT, Salamone J, Freedenberg D, Hannig VL, Prock LA, Miller DT, Raffalli P, Harris DJ, Erickson RP, Cunniff C, Clark GD, Blazo MA, Peiffer DA, Gunderson KL, Sahoo T, Patel A, Lupski JR, Beaudet AL, Cheung SW. Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome region. Genet Med.2007;9:427–41. [PubMed]

6.                      Beunders G, van de Kamp JM, Veenhoven RH, van Hagen JM, Nieuwint AW, Sistermans EA. A triplication of the Williams-Beuren syndrome region in a patient with mental retardation, a