严重程度不同的SHANK2相关神经发育障碍一家系4例基因型-表型关系研究

Genotype-phenotype correlation of four cases of SHANK2-associated neurodevelopmental disorders in a family with different severity

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.