TY - JOUR
T1 - Somatic mosaicism in a mother of two children with Pitt-Hopkins syndrome
AU - Steinbusch, C. V. M.
AU - van Roozendaal, K. E. P.
AU - Tserpelis, D.
AU - Smeets, E. E. J.
AU - Kranenburg-de Koning, T. J.
AU - de Waal, K. H.
AU - Zweier, C.
AU - Rauch, A.
AU - Hennekam, R. C. M.
AU - Blok, M. J.
AU - Schrander-Stumpel, C. T. R. M.
PY - 2013/1
Y1 - 2013/1
N2 - 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. Clin Genet 2013: 83: 73-77. (C) John Wiley & Sons A/S. Published by Blackwell Publishing Ltd, 2012 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.
AB - 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. Clin Genet 2013: 83: 73-77. (C) John Wiley & Sons A/S. Published by Blackwell Publishing Ltd, 2012 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.
KW - familial occurrence
KW - Pitt-Hopkins syndrome
KW - somatic mosaicism
KW - TCF4
U2 - 10.1111/j.1399-0004.2012.01857.x
DO - 10.1111/j.1399-0004.2012.01857.x
M3 - Article
C2 - 22335494
SN - 0009-9163
VL - 83
SP - 73
EP - 77
JO - Clinical Genetics
JF - Clinical Genetics
IS - 1
ER -