神经发育障碍（NDDs）临床异质性强,基因型-表型关系复杂。该研究报道表现为不同程度NDDs,携带SHANK2基因三种变异组合的同一家系患者。该家系2代共4例患者,均表现为轻-重度的智力障碍。遗传学检测发现SHANK2基因变异,包括单等位变异c.2309-2A>C（母亲）、单等位基因11-16外显子缺失（父亲）及同时携带上述双等位基因变异的先证者及其二姐。携带单等位基因缺失变异的父亲表现为轻度智力障碍,携带单等位基因c.2309-2A>C变异的母亲表现为中度智力障碍,而携带双等位基因变异的2例患者均表现为重度智力障碍。SHANK2相关NDDs严重程度可能与SHANK2量依赖相关,此种量依赖现象为理解SHANK2相关NDDs基因型-表型关系提供了帮助。

Neurodevelopmental disorders (NDDs) have strong clinical heterogeneity and complex genotype-phenotype correlation. To improve clinicians' understanding of the genotype-phenotype correlation of SHANK2, this study reported the patients presenting with different degrees of NDDs and carrying three combinations of SHANK2 variations from the same family. A total of 4 patients in the 2 generations of this family showed mild to severe mental retardation. Genetic testing found SHANK2 gene variations, including monoallelic variation c.2309-2A>C (mother) and monoallelic exon 11-16 deletion (father), and two children (the proband and his second sister) who carried the biallelic variations. The father with the monoallelic deletion variation showed mild intellectual disability, the mother with the monoallelic c.2309-2A>C variation showed moderate intellectual disability, and the two patients with the biallelic variations manifested severe intellectual disability. The severity of SHANK2-related NDDs may be associated with SHANK2 quantity dependence, and this quantity dependence provides help for understanding the genotype-phenotype correlation of SHANK2-related NDDs.