CACNA1C haploinsufficiency accounts for the common features of interstitial 12p13.33 deletion carriers

Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations

“…1 Title: Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations Lance H. Rodan MD, 1,2 Rebecca C. Spillmann MS CGC, 3 Harley T. Kurata PhD, 4 Shawn M. Lamothe PhD, 4 Jasmine Maghera BS, 4 Rami Abou Jamra MD, 5 Anna Alkelai PhD, 6 Stylianos E. Antonarakis MD, DSc, 7 Isis Atallah MD, 8 Omer Bar-Yosef MD, PhD, 9,10 Frédéric Bilan PhD, 11 Kathrine Bjorgo MD, 12 Xavier Blanc PhD, 7 Patrick Van Bogaert MD, PhD, 13 Yoav Bolkier MD, 10,14 Lindsay C. Burrage MD, PhD, 15 Björn U. Christ MA, 16 Jorge L. Granadillo MD, 17 Patricia Dickson MD, 17 Kirsten A. Donald MBChB, PhD, 16 Christèle Dubourg PhD, 18,19 Aviva Eliyahu MD, 10,20,21 Lisa Emrick MD, 15 Kendra Engleman MS, CGC, 22 Michaela Veronika Gonfiantini MD, 23 Jean-Marc Good MD, PhD, 24 Judith Kalser MD, 25 Chiara Kloeckner CM, 5 Guus Lachmeijer MD, PhD, 26 Marina Macchiaiolo MD, 23 Francesco Nicita MD, 27 Sylvie Odent MD, 28 Emily O'Heir BS, 1,29 Xilma Ortiz-Gonzalez MD, PhD, 30 Marta Pacio-Miguez MS, 31 María Palomares-Bralo MSc, PhD, 31…”

Variable Phenotypes of Epilepsy, Intellectual Disability, and Schizophrenia Caused by 12p13.33–p13.32 Terminal Microdeletion in a Korean Family: A Case Report and Literature Review

“…To date, approximately 28 reported cases with 12p13.33 microdeletion have been described and are associated with DD/ID and various neuropsychiatric manifestations ( Table 1 ). In these cases [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ], the phenotypic features were variable and indistinct, maybe due to the size of the deleted segment. However, there seems to be no correlation between the size of the deleted size and the severity of the reported clinical phenotypes.…”

“…The Cav1.2 channel plays a part in neurotransmitter release, synaptogenesis, and neuronal excitability; therefore, mutation of CACNA1C is a possible cause of neuropsychiatric disorders [ 33 ]. Recently, the CACNA1C haploinsufficiency was reported to be responsible for the common features of interstitial 12p13.33 deletion carriers [ 23 ]. Furthermore, rs1006737 or the CACNA1C and rs1344706 ZNF804A were commonly associated with schizophrenia and bipolar disorder, and recently with brain phenotypes.…”

“…Constitutional deletions involving the distal part of the short arm of Genes 2021, 12, 1001 2 of 11 chromosome 12 (12p13. 33-p13.32) are very rare and have been reported in only 28 cases so far [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]; either inherited [14,15,17] or sporadic [12,16,17,21,23] and identified by conventional karyotyping or chromosomal microarray (CMA). Notably, among the reported cases, the clinical manifestations differed substantially according to the size of the deletion.…”

“…Fine mapping of the subtelomeric regions has become a new strategy for identifying novel genes responsible for DD and/or ID. Constitutional deletions involving the distal part of the short arm of chromosome 12 (12p13.33–p13.32) are very rare and have been reported in only 28 cases so far [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]; either inherited [ 14 , 15 , 17 ] or sporadic [ 12 , 16 , 17 , 21 , 23 ] and identified by conventional karyotyping or chromosomal microarray (CMA). Notably, among the reported cases, the clinical manifestations differed substantially according to the size of the deletion.…”