Somatic and germ-line mosaicism in Rubinstein-Taybi syndrome
Journal
American Journal of Medical Genetics, Part A
Journal Volume
149
Journal Issue
7
Pages
1463-1467
Date Issued
2009
Author(s)
Abstract
Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant genetic disease and is characterized by mental retardation, distinctive facial features, broad and often angulated thumbs and great toes, short stature, and growth retardation. CREBBP and EP300 are the only genes currently known to be associated with RSTS. Mutations in CREBBP and EP300 were identified in approximately 50% and 3% of RSTS patients, respectively. To date, most ofCREBBPmutations were de novo mutations and the recurrence rate in a family was low. Families with more than one affected child are extremely rare. In this study, we have shown a family with two affected siblings; the same mutation was found in both siblings. However, the mutation was not found in the blood or saliva DNA samples from the parents, suggesting the mechanism of germ-line mosaicism. In addition, we identified low-level mosaicism of a CREBBP mutation in the father from a second family with one affected child. Among the three analyzed tissue samples from the father, low-level mosaicism is present only significantly in the blood sample. We hypothesize mutations in CREBBP in these two families occur in the postzygotic stage in one of the parents (one generation ahead) of the affected individual. Additional family studies are required to determine how common somatic and/or gonadal mosaicism is present in RSTS patients. ? 2009 Wiley-Liss, Inc.
SDGs
Other Subjects
cyclic AMP responsive element binding protein binding protein; DNA; article; birth weight; blood analysis; body height; case report; child; chronic lung disease; cryptorchism; developmental disorder; diabetes insipidus; downward palpebral slant; epidermoid cyst; family study; father; female; gene mutation; germ line; hallux; human; human tissue; hyperglycemia; infant; joint hypermobility; karyotype 46,XX; lacrimal duct occlusion; large for gestational age; lip malformation; low set ear; male; mental deficiency; microcephaly; mosaicism; muscle hypotonia; mutational analysis; nose malformation; nucleotide sequence; palate malformation; patent ductus arteriosus; pilomatrixoma; prematurity; priority journal; Rubinstein syndrome; saliva analysis; school child; sequence analysis; sibling; somatic mutation; speech disorder; stomach fundoplication; thumb malformation; tissue; zygote; CREB-Binding Protein; DNA Mutational Analysis; Family; Female; Germ Cells; Germ-Line Mutation; Humans; Hybrid Cells; Infant, Newborn; Mosaicism; Pedigree; Rubinstein-Taybi Syndrome
Type
journal article