Department of Clinical Genetics, Maastricht UMC, The Netherlands.
Clin Genet. 2013 Jan;83(1):73-7. doi: 10.1111/j.1399-0004.2012.01857.x. Epub 2012 Mar 15.
Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, unusual face and breathing abnormalities and can be caused by haploinsufficiency of TCF4. The majority of cases are sporadic. Somatic mosaicism was reported infrequently. We report on a proband with typical manifestations of PTHS and his younger brother with a less striking phenotype. In both, a heterozygous frameshift mutation (c.1901_1909delinsA, p.Ala634AspfsX67) was found in exon 19 of TCF4. The same mutation was found at low levels in DNA extracted from the mother's blood, urine and saliva. This report of familial recurrence with somatic mosaicism in a healthy mother has important consequences for genetic counseling. We suggest careful studies in parents of other patients with PTHS to determine the frequency of germline and somatic mosaicism for TCF4 mutations.
皮特-霍普金斯综合征（PTHS）是一种神经发育障碍，其特征为智力障碍、异常面容和呼吸异常，可能由 TCF4 单倍不足引起。大多数病例为散发性。体细胞嵌合体报道罕见。我们报告了一个具有典型 PTHS 表现的先证者及其弟弟，其表型不那么明显。在这两兄弟中，均发现 TCF4 外显子 19 中的杂合移码突变（c.1901_1909delinsA，p.Ala634AspfsX67）。在母亲血液、尿液和唾液中提取的 DNA 中也以低水平发现了相同的突变。该报告显示健康母亲中存在家族性复发和体细胞嵌合体，这对遗传咨询具有重要意义。我们建议对其他 PTHS 患者的父母进行仔细研究，以确定 TCF4 突变的种系和体细胞嵌合体的频率。
