Chiara Minotti, Sara Terreri, Andrea Del Fattore, Francesca Romana Lepri, Rosario Ruta, Maria Iascone, Laura Pezzoli, Maria Lisa Dentici, Antonio Novelli, Michelina Armando, Daniela Longo, Giuseppe Novelli, Domenico Barbuti, Andrea Bartuli, Ugo Cavallari, Ludovico Graziani, Maria Cristina Digilio, Lorenzo Sinibaldi
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引用次数: 0
摘要
TRRAP编码参与组蛋白乙酰转移酶复合物的多结构域假激酶。TRRAP致病变异与神经发育障碍、智力残疾、先天性异常和听力损失有关。我们报告了三个不相关的TRRAP错义变体患者。患者1是一名患有严重智力障碍、自闭症特征和轴前多指畸形的女孩,她表现出c.5575C>T, p.(Arg1859Cys)变异。患者2是一名发育迟缓和面部异常的男孩,携带c.5647G> a, p.(Gly1883Arg)变体。患者3是一名患有发育迟缓、癫痫和肾动脉狭窄的女孩,她携带c.8572C>T, p.(Arg2858Trp)变异。这些新病例拓宽了TRRAP表型谱,更新了基因型-表型相关性。我们分析了患者1号的破骨细胞分化和TRRAP在破骨细胞和成骨细胞中的表达,从而假设TRRAP在骨重塑和观察到的骨骼异常中起作用。
Further Exploring the TRRAP Genotype-Phenotype Correlations: Report of Three New Patients With A Focus on Skeletal Anomalies.
TRRAP encodes a multidomain pseudokinase involved in histone acetyltransferase complexes. TRRAP pathogenic variants were linked to neurodevelopmental disorders, intellectual disability, congenital anomalies, and hearing loss. We report on three unrelated patients with TRRAP missense variants. Patient #1, a girl with severe intellectual disability, autism features, and preaxial polydactyly, displays the c.5575C>T, p.(Arg1859Cys) variant. Patient #2, a boy with developmental delay and facial anomalies, harbors the c.5647G>A, p.(Gly1883Arg) variant. Patient #3, a girl with developmental delay, epilepsy, and renal artery stenosis, carries the c.8572C>T, p.(Arg2858Trp) variant. These new cases broaden the TRRAP phenotypic spectrum, updating genotype-phenotype correlations. Osteoclast differentiation in Patient #1 and TRRAP expression in osteoclasts and osteoblasts were analyzed, leading to the assumption of a role of TRRAP in bone remodeling and in the observed skeletal anomalies.
期刊介绍:
Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice.
Topics of particular interest are:
• Linking genetic variations to disease
• Genome rearrangements and disease
• Epigenetics and disease
• The translation of genotype to phenotype
• Genetics of complex disease
• Management/intervention of genetic diseases
• Novel therapies for genetic diseases
• Developmental biology, as it relates to clinical genetics
• Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease