Ding Ning, Zhang Pingping, Mao Yingying, Feng Shuo, Gao Zhijie, Chen Qian, Zhang Xue
Department of Neurology, Children's Hospital, Capital Institute of Pediatrics, Beijing 100020, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2020 Dec 10;37(12):1352-1355. doi: 10.3760/cma.j.cn511374-20191218-00643.
To explore the genetic basis for a pedigree affected with X-linked recessive mental retardation Claes-Jensen type.
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.
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.
The c.1565C>T (p.Ser522Phe) of the KDM5C gene probably underlay the X-linked recessive mental retardation Claes-Jensen type in this pedigree.
探究一个患X连锁隐性克拉斯 - 延森型智力障碍家系的遗传基础。
从患者及其父母（表型正常）以及两名有相似临床表现的哥哥的外周血样本中提取基因组DNA。对先证者进行全外显子组测序，并通过桑格测序验证结果。
在先证者的KDM5C基因第11外显子中发现一个半合子c.1565C>T错义变异。该转换导致第522位丝氨酸被苯丙氨酸取代（p.Ser522Phe）。桑格测序显示患者的两名哥哥和母亲携带相同变异，SIFT、PolyPhen2和Mutation_Taster预测该变异可能具有损害性。三名患病兄弟表现出相似的临床表型，特征为智力障碍、语言发育迟缓、行为问题、药物可控制的自限性癫痫、身材矮小和小头畸形。母亲仅有轻度认知障碍和学习障碍。在他们的父亲中未发现相同变异，且该变异此前未被报道。
KDM5C基因的c.1565C>T（p.Ser522Phe）变异可能是该家系X连锁隐性克拉斯 - 延森型智力障碍的病因。
