Two de novo novel mutations in one SHANK3 allele in a patient with autism and moderate intellectual disability.
Two de novo novel mutations in one SHANK3 allele in a patient with autism and moderate intellectual disability.
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DOI：
10.1002/ajmg.a.38622
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Bi W
中科院分区：
文献类型：
--
作者：
Zhu W;Li J;Chen S;Zhang J;Vetrini F;Braxton A;Eng CM;Yang Y;Xia F;Keller KL;Okinaka-Hu L;Lee C;Holder JL Jr;Bi W
SHANK 3编码将神经递质受体连接到细胞骨架的支架蛋白，并在兴奋性突触的突触后密度中富集。SHANK 3基因的一个拷贝的缺失或突变会导致M-M综合征，也称为22q13.3缺失综合征，这是一种神经发育障碍，其常见特征包括全面发育迟缓，缺乏至严重受损的语言，自闭症行为和轻微的畸形特征。通过全外显子组测序，我们在一名14岁男孩中鉴定了两种从头开始的新变体，包括一种移码突变和一种错义突变，该男孩患有运动里程碑延迟、语言获得延迟、自闭症、智力残疾、共济失调、下肢痉挛进行性恶化、畸形特征、身材矮小、小头畸形、发育不全、慢性便秘，子宫内生长受限和双侧腹股沟疝。这两个变化都在外显子21的CpG岛内，由287 bp序列分开。PCR产物的下一代测序显示，这两种变体最常相互关联。克隆PCR产物的桑格测序进一步证实了两种变化都在单个等位基因上。该患者的临床表现与其他21号外显子截短突变患者一致，表明错义突变对表型无贡献或贡献极小。这是首次报道在一个SHANK 3等位基因中发生两个新突变。
SHANK3 encodes for a scaffolding protein that links neurotransmitter receptors to the cytoskeleton and is enriched in postsynaptic densities of excitatory synapses. Deletions or mutations in one copy of the SHANK3 gene cause Phelan-McDermid syndrome, also called 22q13.3 deletion syndrome, a neurodevelopmental disorder with common features including global developmental delay, absent to severely impaired language, autistic behavior, and minor dysmorphic features. By whole exome sequencing, we identified two de novo novel variants including one frameshift mutation and one missense change in a 14-year-old boy with delayed motor milestones, delayed language acquisition, autism, intellectual disability, ataxia, progressively worsening spasticity of the lower extremities, dysmorphic features, short stature, microcephaly, failure to thrive, chronic constipation, intrauterine growth restriction and bilateral inguinal hernias. Both changes are within the CpG island in exon 21, separated by a 287 bp sequence. Next generation sequencing of PCR products revealed that the two variants are most frequently associated with each other. Sanger sequencing of the cloned PCR products further confirmed that both changes were on a single allele. The clinical presentation in this individual is consistent with other patients with a truncating mutation in exon 21, suggesting that the missense change contributes none or minimally to the phenotypes. This is the first report of two de novo mutations in one SHANK3 allele.
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影响因子：
11
作者：
Durand CM;Perroy J;Loll F;Perrais D;Fagni L;Bourgeron T;Montcouquiol M;Sans N
通讯作者：
Sans N
影响因子：
4.7
作者：
Boeckers, TM;Liedtke, T;Gundelfinger, ED
通讯作者：
Gundelfinger, ED
影响因子：
5.2
作者：
Boccuto, Luigi;Lauri, Maria;Schwartz, Charles E.
通讯作者：
Schwartz, Charles E.
影响因子：
5.8
作者：
Tessitore, A;Sinisi, AA;Colantuoni, V
通讯作者：
Colantuoni, V
DOI：
10.1073/pnas.0906232107
发表时间：
2010-04-27
影响因子：
11.1
作者：
Gauthier, Julie;Champagne, Nathalie;Rouleau, Guy A.
通讯作者：
Rouleau, Guy A.