Atypical development of Broca's area in a large family with inherited stuttering.
Atypical development of Broca's area in a large family with inherited stuttering.
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患有遗传性口吃的大家庭中布罗卡区的非典型发育。
DOI：
10.1093/brain/awab364
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Morgan,AngelaT
中科院分区：
文献类型：
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作者：
Thompson-Lake,DaisyGY;Scerri,ThomasS;Block,Susan;Turner,SamanthaJ;Reilly,Sheena;Kefalianos,Elaina;Bonthrone,AlexandraF;Helbig,Ingo;Bahlo,Melanie;Scheffer,IngridE;Hildebrand,MichaelS;Liégeois,FrédériqueJ;Morgan,AngelaT
发展性口吃是一种语言不流畅的状况，其特征是停顿、阻塞、延长和声音或音节重复。它影响了大约1%的人口，对心理健康和长期就业有潜在的有害影响。越来越多的证据指向遗传病因，但由于缺乏对受影响家庭的MRI研究，基因与大脑的关联仍然知之甚少。在这里，我们报告了一个常染色体显性遗传持续性口吃家庭的发展性口吃的首次神经影像学研究。我们研究了一个4代家庭，包括16名家庭成员进行基因分型分析。对7名家庭成员（6名男性，年龄9-63岁）进行t1加权和弥散加权MRI扫描，并与2名年龄和性别匹配的对照组进行对照，无口吃（n= 14）。使用Freesurfer，我们分析了皮质形态（皮质厚度、表面积和局部回转指数）和基底神经节体积。使用磁共振成像和概率束图分析了关键言语和语言束（即额斜束和弓状束）的白质完整性。我们发现了一个显著的年龄组相互作用的影响皮层厚度在左半球包部（布洛卡区）。在受影响的家庭成员中，该区域未能遵循在对照组中观察到的与年龄相关的典型变薄轨迹。表面面积分析显示，该家族的额叶中回区域双侧减少（所有皮质形态学显著性水平设置在顶点方向阈值p < 0.01，经多次比较校正）。该家族患儿左、右苍白球均大于对照组（leftP= 0.017；右P= 0.037），且右苍白球越大口吃越严重（rho = 0.86，P= 0.01）。未发现白质差异。基因分型鉴定出1号和4号染色体上与口吃表型相关的新位点。我们的发现表明在皮质-基底神经节-丘脑-皮质网络中存在破坏。这些结构缺乏典型的发育，反映了在这些个体中支撑口吃的布洛卡区和纹状体之间异常抑制控制网络的解剖学基础。这是常染色体显性遗传口吃家族中神经表型的第一个证据。
Developmental stuttering is a condition of speech dysfluency, characterized by pauses, blocks, prolongations and sound or syllable repetitions. It affects around 1% of the population, with potential detrimental effects on mental health and long-term employment. Accumulating evidence points to a genetic aetiology, yet gene–brain associations remain poorly understood due to a lack of MRI studies in affected families. Here we report the first neuroimaging study of developmental stuttering in a family with autosomal dominant inheritance of persistent stuttering.We studied a four-generation family, 16 family members were included in genotyping analysis. T1-weighted and diffusion-weighted MRI scans were conducted on seven family members (six male; aged 9–63 years) with two age and sex matched controls without stuttering (n= 14). Using Freesurfer, we analysed cortical morphology (cortical thickness, surface area and local gyrification index) and basal ganglia volumes. White matter integrity in key speech and language tracts (i.e. frontal aslant tract and arcuate fasciculus) was also analysed using MRtrix and probabilistic tractography.We identified a significant age by group interaction effect for cortical thickness in the left hemisphere pars opercularis (Broca’s area). In affected family members this region failed to follow the typical trajectory of age-related thinning observed in controls. Surface area analysis revealed the middle frontal gyrus region was reduced bilaterally in the family (all cortical morphometry significance levels set at a vertex-wise threshold ofP< 0.01, corrected for multiple comparisons). Both the left and right globus pallidus were larger in the family than in the control group (leftP= 0.017; rightP= 0.037), and a larger right globus pallidus was associated with more severe stuttering (rho = 0.86,P= 0.01). No white matter differences were identified. Genotyping identified novel loci on chromosomes 1 and 4 that map with the stuttering phenotype.Our findings denote disruption within the cortico-basal ganglia-thalamo-cortical network. The lack of typical development of these structures reflects the anatomical basis of the abnormal inhibitory control network between Broca’s area and the striatum underpinning stuttering in these individuals. This is the first evidence of a neural phenotype in a family with an autosomal dominantly inherited stuttering.