title: Somatic mosaicism in a mother of two children with Pitt-Hopkins syndrome.
abstract: 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.
authors.affiliation: Department of Clinical Genetics, Maastricht UMC, The Netherlands.
authors.forename: C V M
authors.initials: CV
authors.lastname: Steinbusch
authors.forename: K E P
authors.initials: KE
authors.lastname: van Roozendaal
authors.forename: D
authors.initials: D
authors.lastname: Tserpelis
authors.forename: E E J
authors.initials: EE
authors.lastname: Smeets
authors.forename: T J
authors.initials: TJ
authors.lastname: Kranenburg-de Koning
authors.forename: K H
authors.initials: KH
authors.lastname: de Waal
authors.forename: C
authors.initials: C
authors.lastname: Zweier
authors.forename: A
authors.initials: A
authors.lastname: Rauch
authors.forename: R C M
authors.initials: RC
authors.lastname: Hennekam
authors.forename: M J
authors.initials: MJ
authors.lastname: Blok
authors.forename: C T R M
authors.initials: CT
authors.lastname: Schrander-Stumpel
mesh_terms: D000328:Adult; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000097:blood / Q000235:genetics* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D019066:Facies; D005260:Female; D016368:Frameshift Mutation; D005817:Genetic Counseling; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D006985:Hyperventilation / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000652:urine; D008607:Intellectual Disability / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000652:urine; D008297:Male; D009030:Mosaicism; D009035:Mothers; D010641:Phenotype; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000097:blood / Q000235:genetics* / Q000652:urine
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors