2q24 deletions: Further characterization of clinical findings and their relation to the SCN cluster

作者：Nimmakayalu Manjunath; Noble Nathan; Horton V Kim; Willing Marcia; Copeland Sara; Sheffield Val; Nagy Peter L; Wassink Tom; Patil Shivanand; Shchelochkov Oleg A^*

来源：American Journal of Medical Genetics, Part A, 2012, 158A(11): 2767-2774.

DOI：10.1002/ajmg.a.35362

• 2q24
• 2q31
• 1
• seizures
• growth retardation
• microcephaly
• Dravet syndrome
• SCN cluster
• SCN3A
• SCN2A
• SCN1A
• SCN9A
• SCN7A
• SLC4A10
• FIGN
• array comparative genomic hybridization (aCGH)

As the resolution of molecular cytogenetic methods continues to improve, it has become increasingly possible to refine genotypephenotype 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 8?Mb 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, similar to 8?Mb and %26lt;500?kb 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.

• 出版日期2012-11