Sciacca Francesca L, Ciaccio Claudia, Fontana Federica, Strano Camilla, Gilardoni Francesca, Pantaleoni Chiara, D'Arrigo Stefano
Neurological Biochemistry and Neuropharmacology Unit, Laboratory of Cytogenetic, Department of Diagnostic and Technology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Front Genet. 2020 May 13;11:399. doi: 10.3389/fgene.2020.00399. eCollection 2020.
Homozygous and compound heterozygous mutations in gene have been associated with a wide spectrum of clinical presentations, ranging from neurodevelopmental issues with or without cardiac arrhythmia (LADCI) to severe developmental delay with epileptic encephalopathy, retinal dystrophy, and heart rhythm abnormalities (IDDCA). While missense or missense/non-sense mutations usually lead to milder form, the biallelic loss of function of 5 gene causes the severe multisystemic IDDCA phenotype. So far, only 27 patients have been described with -associated disease. We report the first case of a patient carrying a homozygous 15q21.2 microdeletion, encompassing and the two contiguous genes and . The clinical features of the child are consistent with the severe IDDCA phenotype, thus confirming the loss-of-function mechanism in determining such presentation of the disease.
该基因的纯合和复合杂合突变与广泛的临床表现相关，范围从伴有或不伴有心律失常的神经发育问题（LADCI）到伴有癫痫性脑病、视网膜营养不良和心律异常的严重发育迟缓（IDDCA）。虽然错义或错义/无义突变通常导致较轻的形式，但该基因双等位基因功能丧失会导致严重的多系统IDDCA表型。到目前为止，仅有27例与该基因相关疾病的患者被报道。我们报告了首例携带纯合15q21.2微缺失的患者，该微缺失包含该基因以及两个相邻基因。该患儿的临床特征与严重的IDDCA表型一致，从而证实了该基因功能丧失机制在决定该疾病此种表现中的作用。
