Pajusalu Sander, Reimand Tiia, Õunap Katrin
Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia.
Am J Med Genet A. 2015 Aug;167A(8):1913-5. doi: 10.1002/ajmg.a.37105. Epub 2015 Apr 5.
Recently, a novel autosomal recessive developmental delay-macrocephaly syndrome was described caused by homozygous or compound heterozygous mutations in the KPTN gene. All reported patients belonged to one large Amish kindred. We report on the second case of KPTN-related syndrome in two Estonian adult sibs. The brother and sister both have macrocephaly and moderate intellectual disability, and their verbal abilities are more affected than motor development. No notable minor anomalies are present. Behavioral problems and a few episodes of seizures were reported in the brother. Whole exome sequencing carried out from the brother's DNA sample identified homozygous one-nucleotide frameshift duplication c.665dupA (p.Q222fs) in the KPTN gene. Homozygosity of both affected sibs and heterozygosity of parents were confirmed by Sanger sequencing. Thus, we confirm the pathogenicity of KPTN mutations and further delineate the novel developmental delay-macrocephaly syndrome. We also support the hypothesis that KPTN-related syndrome is not restricted to the Amish population.
最近，一种由KPTN基因纯合或复合杂合突变引起的新型常染色体隐性发育迟缓-巨头综合征被报道。所有报告的患者都属于一个大型阿米什家族。我们报告了爱沙尼亚两名成年同胞中第二例与KPTN相关的综合征病例。这对兄妹都有巨头症和中度智力障碍，他们的语言能力比运动发育受影响更大。没有明显的轻微异常。哥哥报告有行为问题和几次癫痫发作。对哥哥的DNA样本进行的全外显子组测序在KPTN基因中鉴定出纯合的单核苷酸移码重复c.665dupA（p.Q222fs）。通过桑格测序证实了两名患病同胞的纯合性和父母的杂合性。因此，我们证实了KPTN突变的致病性，并进一步描述了这种新型的发育迟缓-巨头综合征。我们还支持这样一种假设，即与KPTN相关的综合征并不局限于阿米什人群。
