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Abstract：
Intellectual developmental disorder with abnormal behavior, microcephaly and short stature (IDDABS), (OMIM# 618342) is an autosomal recessive condition described as developmental delay, poor or absent speech, intellectual disability, short stature, mild to progressive microcephaly, delayed psychomotor development, hyperactivity, seizure, along with mild to swear aggressive behavior. Homozygous frameshift mutation in Pseudouridine Synthase 7, Putative; (PUS7) OMIM# 616,261 NM_019042.3 and splice acceptor variants in Alpha-Aminoadipic Semialdehyde Synthase; (AASS) OMIM# 605,113 NM_005763.3 was funded. Whole exome sequencing (WES) technique was used as tool to identify the molecular diagnostic test. Different bioinformatics analysis done for WES data and we identified two novel mutations one as frameshift mutation c.606_607delGA, p.Ser282CysfsTer9 in the PUS7 gene and splice acceptor variants c.1767-1 G > A in the AASS gene has been reported. The pattern of family segregation maintained the pathogenicity of this variation associated with abnormal behavior, intellectual developmental disorder, microcephaly along with short stature IDDABS. Further, the WES data was validated in the family having other affected individuals and healthy controls (n = 100) was done using Sanger sequencing. Finally, our results further explained the role of WES in the disease diagnosis and elucidated that the mutation in PUS7 and AASS genes may lead an important role for the development of IDDABS in Saudi family.
摘要：
具有异常行为的智力发育障碍，小头畸形和身材矮小（IDDABS），（OMIM＃618342）是一种常染色体隐性遗传疾病，被描述为发育迟缓，糟糕或缺席的演讲，智力残疾,身材矮小,轻度至进行性小头畸形，精神运动发育延迟，多动症,癫痫发作,以及温和的发誓攻击性行为。伪尿苷合成酶7的纯合移码突变，推定；（PUS7）OMIM＃616,261NM_019042.3和α-氨基己二酸半醛合成酶中的剪接受体变体；（AASS）OMIM＃605,113NM_005763.3得到资助。使用全外显子组测序（WES）技术作为鉴定分子诊断测试的工具。对WES数据进行了不同的生物信息学分析，我们确定了两个新的突变，一个是移码突变c.606_607delGA，已经报道了PUS7基因中的p.Ser282CysfsTer9和AASS基因中的剪接受体变体c.1767-1G>A。家族分离的模式维持了与异常行为相关的这种变异的致病性，智力发育障碍,小头畸形伴身材矮小的IDDABS。Further,使用Sanger测序在有其他受影响个体和健康对照(n=100)的家庭中验证了WES数据.最后,我们的研究结果进一步解释了WES在疾病诊断中的作用,并阐明了PUS7和AASS基因突变可能在沙特家族IDDABS的发展中起重要作用.
