Somatic and germ-line mosaicism in Rubinstein-Taybi syndrome

Pei-Wen Chiang, Ni Chung Lee, Nancy Chien, Wuh Liang Hwu, Elaine Spector, Anne Tsai

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1463-1467
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Volume149
Issue number7
DOIs
StatePublished - Jul 2009
Externally publishedYes

Fingerprint

Rubinstein-Taybi Syndrome
Mosaicism
Germ Cells
Mutation
Fathers
Siblings
Parents
Hallux
Inborn Genetic Diseases
Thumb
Mutation Rate
Saliva
Intellectual Disability
Recurrence
DNA
Growth

Keywords

  • CREBBP
  • EP300
  • Mosaicism
  • RSTS
  • Rubinstein-Taybi syndrome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Chiang, P-W., Lee, N. C., Chien, N., Hwu, W. L., Spector, E., & Tsai, A. (2009). Somatic and germ-line mosaicism in Rubinstein-Taybi syndrome. American Journal of Medical Genetics, Part A, 149(7), 1463-1467. https://doi.org/10.1002/ajmg.a.32948

Somatic and germ-line mosaicism in Rubinstein-Taybi syndrome. / Chiang, Pei-Wen; Lee, Ni Chung; Chien, Nancy; Hwu, Wuh Liang; Spector, Elaine; Tsai, Anne.

In: American Journal of Medical Genetics, Part A, Vol. 149, No. 7, 07.2009, p. 1463-1467.

Research output: Contribution to journalArticle

Chiang, P-W, Lee, NC, Chien, N, Hwu, WL, Spector, E & Tsai, A 2009, 'Somatic and germ-line mosaicism in Rubinstein-Taybi syndrome', American Journal of Medical Genetics, Part A, vol. 149, no. 7, pp. 1463-1467. https://doi.org/10.1002/ajmg.a.32948
Chiang, Pei-Wen ; Lee, Ni Chung ; Chien, Nancy ; Hwu, Wuh Liang ; Spector, Elaine ; Tsai, Anne. / Somatic and germ-line mosaicism in Rubinstein-Taybi syndrome. In: American Journal of Medical Genetics, Part A. 2009 ; Vol. 149, No. 7. pp. 1463-1467.
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