Dunkerton Sophie, Field Matthew, Cho Vicki, Bertram Edward, Whittle Belinda, Groves Alexandra, Goel Himanshu
University of Newcastle, Callaghan, New South Wales, Australia.
Department of Immunology, John Curtin School of Medical Research, Australian National University, Canberra City, Australian Capital Territory, Australia.
Am J Med Genet A. 2015 Sep;167A(9):2182-7. doi: 10.1002/ajmg.a.37130. Epub 2015 Apr 30.
Growth deficiency, psychomotor delay, and facial dysmorphism was originally described in a male patient in 1989 by Wiedemann et al. and later in 2000 by Steiner et al. Wiedemann-Steiner syndrome (WSS) has since been described only a few times in the literature, with the phenotypic spectrum both expanding and becoming more delineated with each patient reported. We report on the clinical and molecular features of monozygotic twins with a de novo mutation in KMT2A. Single nucleotide polymorphism (SNP) microarray was done on both twins and whole-exome sequencing was done using both parents and one of the affected twins. SNP microarray confirmed that they were monozygotic twins. A de novo heterozygous variant (p. Arg1083*) in the KMT2A gene was identified through whole-exome sequencing, confirming the diagnosis of WSS. In this study, we have identified a de novo mutation in KMT2A associated with psychomotor developmental delay, facial dysmorphism, short stature, hypertrichosis cubiti, and small kidneys. This finding in monozygotic twins gives specificity to the WSS. The description of more cases of WSS is needed for further delineation of this condition. Small kidneys with normal function have not been described in this condition in the medical literature before.
生长发育迟缓、精神运动发育迟缓和面部畸形最初于1989年由维德曼等人在一名男性患者中描述，后来于2000年由施泰纳等人描述。自那时以来，维德曼-施泰纳综合征（WSS）在文献中仅有少数报道，随着每例报道患者的出现，其表型谱不断扩展且愈发清晰。我们报告了一对单卵双胞胎的临床和分子特征，他们的KMT2A基因发生了新发突变。对双胞胎均进行了单核苷酸多态性（SNP）微阵列检测，并使用父母和其中一名患病双胞胎进行了全外显子组测序。SNP微阵列证实他们是单卵双胞胎。通过全外显子组测序鉴定出KMT2A基因中的一个新发杂合变异（p.Arg1083*），从而确诊为WSS。在本研究中，我们鉴定出KMT2A基因中的一个新发突变，该突变与精神运动发育迟缓、面部畸形、身材矮小、肘部多毛症和小肾脏有关。单卵双胞胎中的这一发现明确了WSS的特征。需要描述更多WSS病例以进一步明确这种疾病。医学文献中此前尚未描述过功能正常的小肾脏这种情况。
