Somatic mosaicism in a mother of two children with Pitt–Hopkins syndrome. (15th March 2012)

• Record Type: Journal Article
• Authors: Steinbusch, CVM; van Roozendaal, KEP; Tserpelis, D; Smeets, EEJ; Kranenburg‐de Koning, TJ; de Waal, KH; Zweier, C; Rauch, A; Hennekam, RCM; Blok, MJ; Schrander‐Stumpel, CTRM
• Is Part Of: Clinical genetics. Volume 83:Number 1(2013:Jan.)
• Page Start: 73
• Page End: 77
• Publication Date: 2012-03-15
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/j.1399-0004.2012.01857.x
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Steinbusch CVM, van Roozendaal KEP, Tserpelis D, Smeets EEJ, Kranenburg‐de Koning TJ, de Waal KH, Zweier C, Rauch A, Hennekam RCM, Blok MJ, Schrander‐Stumpel CTRM. Somatic mosaicism in a mother of two children with Pitt–Hopkins syndrome.</p> <p>Pitt–Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, unusual face and breathing abnormalities and can be caused by haploinsufficiency of <italic>TCF4</italic>. 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 <italic>TCF4</italic>. 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 <italic>TCF4</italic> mutations.</p> </abstract>