TY - JOUR
T1 - 2q24 deletions
T2 - Further characterization of clinical findings and their relation to the SCN cluster
AU - Nimmakayalu, Manjunath
AU - Noble, Nathan
AU - Horton, V. Kim
AU - Willing, Marcia
AU - Copeland, Sara
AU - Sheffield, Val
AU - Nagy, Peter L.
AU - Wassink, Tom
AU - Patil, Shivanand
AU - Shchelochkov, Oleg A.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/11
Y1 - 2012/11
N2 - As the resolution of molecular cytogenetic methods continues to improve, it has become increasingly possible to refine genotype-phenotype correlations based upon gene involvement. We report three new patients with nonrecurrent deletions involving subbands of 2q24. These patients were referred for evaluation of developmental delay, but were found to have unique, nonoverlapping clinical features. Patient 1 presented with infantile seizures, microcephaly, and brain anomalies, along with facial dysmorphism, growth retardation, neuromuscular scoliosis, and later with developmental regression. Array comparative genomic hybridization (aCGH) detected an 8Mb interstitial deletion encompassing the neuronal sodium channel (SCN) gene cluster. Patient 2 presented with growth retardation, congenital heart defect, and hypotonia. Patient 3 presented with developmental delay and behavioral problems. Patients 2 and 3 had no history of seizures, microcephaly, or brain anomalies and were found to have deletions of 2q24, ~8Mb and <500kb respectively, centromeric to and outside the SCN cluster. It has been demonstrated that mutations and copy number variants (CNVs) affecting the SCN gene cluster result in severe, early-onset seizures. It is however, less clear whether haploinsufficiency of regions outside the SCN cluster may result in phenotypically recognizable and clinically significant features. We discuss additional dosage sensitive genes that may exist outside the SCN cluster. Our and published data indicate that 2q24 deletions not involving the SCN cluster are associated with fewer neurobehavioral problems, but may predispose to congenital malformations.
AB - As the resolution of molecular cytogenetic methods continues to improve, it has become increasingly possible to refine genotype-phenotype correlations based upon gene involvement. We report three new patients with nonrecurrent deletions involving subbands of 2q24. These patients were referred for evaluation of developmental delay, but were found to have unique, nonoverlapping clinical features. Patient 1 presented with infantile seizures, microcephaly, and brain anomalies, along with facial dysmorphism, growth retardation, neuromuscular scoliosis, and later with developmental regression. Array comparative genomic hybridization (aCGH) detected an 8Mb interstitial deletion encompassing the neuronal sodium channel (SCN) gene cluster. Patient 2 presented with growth retardation, congenital heart defect, and hypotonia. Patient 3 presented with developmental delay and behavioral problems. Patients 2 and 3 had no history of seizures, microcephaly, or brain anomalies and were found to have deletions of 2q24, ~8Mb and <500kb respectively, centromeric to and outside the SCN cluster. It has been demonstrated that mutations and copy number variants (CNVs) affecting the SCN gene cluster result in severe, early-onset seizures. It is however, less clear whether haploinsufficiency of regions outside the SCN cluster may result in phenotypically recognizable and clinically significant features. We discuss additional dosage sensitive genes that may exist outside the SCN cluster. Our and published data indicate that 2q24 deletions not involving the SCN cluster are associated with fewer neurobehavioral problems, but may predispose to congenital malformations.
KW - 2q24
KW - 2q31.1
KW - Array comparative genomic hybridization (aCGH)
KW - Dravet syndrome
KW - FIGN
KW - Growth retardation
KW - Microcephaly
KW - SCN cluster
KW - SCN1A
KW - SCN2A
KW - SCN3A
KW - SCN7A
KW - SCN9A
KW - SLC4A10
KW - Seizures
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U2 - 10.1002/ajmg.a.35362
DO - 10.1002/ajmg.a.35362
M3 - Article
C2 - 23023937
AN - SCOPUS:84867870734
SN - 1552-4825
VL - 158 A
SP - 2767
EP - 2774
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 11
ER -