摘要目的:对1个X连锁隐性遗传精神发育迟滞Claes-Jensen型家系进行 KDM5C基因变异分析，明确其致病原因。 方法:采集先证者及其父母兄弟共5人外周血，进行全外显子测序，Sanger测序验证。结果:测序结果提示先证者为 KDM5C基因第11外显子c.1565C>T(p.Ser522Phe)半合子错义变异，Sanger测序验证其两兄长也为c.1565C>T(p.Ser522Phe)变异的半合子，母亲为c.1565C>T(p.Ser522Phe)变异杂合子，父亲未检测到 KDM5C基因变异。c.1565C>T(p.Ser522Phe)变异引起患儿及其两兄长精神发育迟滞、癫痫、身材矮小、小头畸形，母亲有轻度认知障碍和学习困难。 KDM5C基因第11外显子c.1565C>T(p.Ser522Phe)变异是一种未见报道过的致病变异。 结论:KDM5C第11外显子c.1565C>T变异是本患儿家系的致病原因。

abstractsObjective:To explore the genetic basis for a pedigree affected with X-linked recessive mental retardation Claes-Jensen type.Methods:Genomic DNA was extracted from peripheral blood samples of the patient, his parents (phenotypically normal) and two elder brothers with similar clinical manifestations. Whole exome sequencing was carried out for the proband, and the result was verified by Sanger sequencing.Results:The proband was found to harbor a hemizygous c. 1565C>T missense variant in exon 11 of the KDM5C gene. The transition has resulted in replacement of serine by phenylalanine at position 522 (p.Ser522Phe). Sanger sequencing showed that the patient’s two elder brothers and mother carried the same variant, which was predicted to be probably damaging by SIFT, PolyPhen2 and Mutation_Taster. The three affected brothers presented with similar clinical phenotypes characterized by mental retardation, speech delay, behavioral problem, self-limited epilepsy responsible to medication, short stature and microcephaly. The mother only had mild cognitive impairment and learning disability. The same variant was not found in their father and was unreported previously. Conclusion:The c. 1565C>T (p.Ser522Phe) of the KDM5C gene probably underlay the X-linked recessive mental retardation Claes-Jensen type in this pedigree.