TY - JOUR
T1 - Genotype-phenotype correlation in interstitial 6q deletions
T2 - A report of 12 new cases
AU - Rosenfeld, Jill A.
AU - Amrom, Dina
AU - Andermann, Eva
AU - Andermann, Frederick
AU - Veilleux, Martin
AU - Curry, Cynthia
AU - Fisher, Jamie
AU - Deputy, Stephen
AU - Aylsworth, Arthur S.
AU - Powell, Cynthia M.
AU - Manickam, Kandamurugu
AU - Heese, Bryce
AU - Maisenbacher, Melissa
AU - Stevens, Cathy
AU - Ellison, Jay W.
AU - Upton, Sheila
AU - Moeschler, John
AU - Torres-Martinez, Wilfredo
AU - Stevens, Abby
AU - Marion, Robert
AU - Pereira, Elaine Maria
AU - Babcock, Melanie
AU - Morrow, Bernice
AU - Sahoo, Trilochan
AU - Lamb, Allen N.
AU - Ballif, Blake C.
AU - Paciorkowski, Alex R.
AU - Shaffer, Lisa G.
PY - 2012/2
Y1 - 2012/2
N2 - Interstitial deletions of 6q are associated with variable phenotypes, including growth retardation, dysmorphic features, upper limb malformations, and Prader-Willi (PW)-like features. Only a minority of cases in the literature have been characterized with high resolution techniques, making genotype-phenotype correlations difficult. We report 12 individuals with overlapping, 200-kb to 16.4-Mb interstitial deletions within 6q15q22.33 characterized by microarray-based comparative genomic hybridization to better correlate deletion regions with specific phenotypes. Four individuals have a PW-like phenotype, though only two have deletion of SIM1, the candidate gene for thisfeature. Therefore, other genes on 6q may contribute to this phenotype including multiple genes on 6q16 and our newly proposed candidate, the transcription cofactor gene VGLL2 on 6q22.2. Two individuals present with movement disorders as a major feature, and ataxia is present in a third. The 4.1-Mb 6q22.1q22.2 critical region for movement disorders includes the cerebellar-expressed candidate gene GOPC. Observed brain malformations include thick corpus callosum in two subjects, cerebellar vermal hypoplasia in two subjects, and cerebellar atrophy in one subject. Seven subjects' deletions overlap a ~250-kb cluster of four genes on 6q22.1 including MARCKS, HDAC2, and HS3ST5, which are involved in neural development. Two subjects have only this gene cluster deleted, and one deletion was apparently de novo, suggesting at least one of these genes plays an important role in development. Although the phenotypes associated with 6q deletions can vary, using overlapping deletions to delineate critical regions improves genotype - phenotype correlation for interstitial 6q deletions.
AB - Interstitial deletions of 6q are associated with variable phenotypes, including growth retardation, dysmorphic features, upper limb malformations, and Prader-Willi (PW)-like features. Only a minority of cases in the literature have been characterized with high resolution techniques, making genotype-phenotype correlations difficult. We report 12 individuals with overlapping, 200-kb to 16.4-Mb interstitial deletions within 6q15q22.33 characterized by microarray-based comparative genomic hybridization to better correlate deletion regions with specific phenotypes. Four individuals have a PW-like phenotype, though only two have deletion of SIM1, the candidate gene for thisfeature. Therefore, other genes on 6q may contribute to this phenotype including multiple genes on 6q16 and our newly proposed candidate, the transcription cofactor gene VGLL2 on 6q22.2. Two individuals present with movement disorders as a major feature, and ataxia is present in a third. The 4.1-Mb 6q22.1q22.2 critical region for movement disorders includes the cerebellar-expressed candidate gene GOPC. Observed brain malformations include thick corpus callosum in two subjects, cerebellar vermal hypoplasia in two subjects, and cerebellar atrophy in one subject. Seven subjects' deletions overlap a ~250-kb cluster of four genes on 6q22.1 including MARCKS, HDAC2, and HS3ST5, which are involved in neural development. Two subjects have only this gene cluster deleted, and one deletion was apparently de novo, suggesting at least one of these genes plays an important role in development. Although the phenotypes associated with 6q deletions can vary, using overlapping deletions to delineate critical regions improves genotype - phenotype correlation for interstitial 6q deletions.
KW - 6q deletion
KW - Epilepsy
KW - Microarray
KW - Microcephaly
KW - Movement disorders
KW - Prader - Willi-like phenotype
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UR - http://www.scopus.com/inward/citedby.url?scp=84861418024&partnerID=8YFLogxK
U2 - 10.1007/s10048-011-0306-5
DO - 10.1007/s10048-011-0306-5
M3 - Article
C2 - 22218741
AN - SCOPUS:84861418024
SN - 1364-6745
VL - 13
SP - 31
EP - 47
JO - Neurogenetics
JF - Neurogenetics
IS - 1
ER -