Germline mosaicism in Rubinstein-Taybi syndrome.

Mariam Tajir, Patricia Fergelot, Guenaelle Lancelot, Siham Chafai Elalaoui, Benoit Arveiler, Didier Lacombe, Abdelaziz Sefiani

Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohamed V Souissi, Rabat, Maroc. mariam_tajir@yahoo.fr

Gene 2013 Apr 15

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Rubinstein-Taybi syndrome is an autosomal dominant disorder with multiple congenital anomalies and genetic heterogeneity. Clinical manifestations include mental retardation, postnatal growth deficiency, microcephaly, broad thumbs and halluces, and characteristic facial features. Mutations in the gene encoding the transcriptional coactivator CREB-binding protein (CREBBP; OMIM 600140) on chromosome 16p13, account for about 50% to 70% of patients. Most of CREBBP mutations are de novo and the rate of recurrence in a family is low. Families with several affected children are extremely rare. We report here a Moroccan family with two children with RSTS and apparently unaffected parents. The molecular studies showed a heterozygous mutation c.4361T>A (p.Leu1454His) in exon 26 of the CREBBP gene in the two affected siblings. Neither the parents, nor the healthy brother, carry this mutation in hematologic cells. The mutation was also absent in buccal epithelial cells of both parents. We discuss the hypothesis of germinal mosaicism. This concept is very important because it complicates genetic counseling of this family who has a risk of recurrence of the mutation in subsequent pregnancies. Copyright © 2013 Elsevier B.V. All rights reserved.

Citation

Mariam Tajir, Patricia Fergelot, Guenaelle Lancelot, Siham Chafai Elalaoui, Benoit Arveiler, Didier Lacombe, Abdelaziz Sefiani. Germline mosaicism in Rubinstein-Taybi syndrome. Gene. 2013 Apr 15;518(2):476-8