Somatic and germ-line mosaicism in Rubinstein-Taybi syndrome.
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 of CREBBP mutations 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.
Chiang
Pei-Wen
PW
Department of Pediatrics, UC Denver DNA Diagnostic Laboratory, UC Denver School of Medicine, Aurora, Colorado, USA.
Lee
Ni-Chung
NC
Chien
Nancy
N
Hwu
Wuh-Liang
WL
Spector
Elaine
E
Tsai
Anne Chun-Hui
AC
D050882:CREB-Binding Protein / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005854:Germ Cells / Q000378:metabolism / Q000473:pathology*; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism / Q000473:pathology*; D007231:Infant, Newborn; D009030:Mosaicism; D010375:Pedigree; D012415:Rubinstein-Taybi Syndrome / Q000235:genetics / Q000473:pathology
D050882:CREB-Binding Protein; C494363:CREBBP protein, human