A 261 kb deletion spanning three genes is causing Rubinstein-Taybi syndrome type 1 in a 6-year-old boy belonging to...

Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomaly/intellectual disability characterized by growth and psychomotor development delays, hallux thumbs, characteristic facial dysmorphisms with down slanting palpebral fissures, thin upper lip, high nasal bridge, arched eyebrows, micrognathia and a higher risk of tumour formation. RSTS type 1 (RSTS-1) is caused by variants of CREBBP encoding CREB-binding protein which act as transcriptional co-activators and variants of its paralog EP300 that code for E1A associated protein p300 results in RSTS type 2 (RSTS-2). CREBBP and EP300 mutations have been identified in majority (50-60 %) and minority (3-5 %) of RSTS affected individuals. It is a rare autosomal dominant disorder that affects 1 in 300,000 births. Rare diseases (RDs) are progressive, chronically debilitating and/or life-threatening heterogeneous clinical conditions that affect a limited fraction. In this article, we report a case of Rubinstein-Taybi syndrome type 1, a six-year-old boy (proband) belonging to Srinagar district of the Union Territory of Jammu and Kashmir (J&K), India established on the basis of phenotypic symptoms and radiological findings. Whole Exome Sequencing and further Array Comparative Genome Hybridization confirmed the presence of a de novo copy number variation with a 261 kb heterozygous microdeletion present on 16p13.3 cytoband (Chr16:3,694,760-3,955,374) (GRCh37/hg19) spanning three genes DNASE1 (OMIM #125505), TRAP1 (OMIM# 606219) and CREBBP (OMIM# 600140) in the proband only and missing in parents. This is a novel de novo microdeletion being reported for the first time. Haploinsufficiency resulting from copy number loss, indicated by 0.78-fold decreased expression of the CREBBP gene in patient compared to parents is resulting in the development of the disease.