Reduced expression by SETBP1 haploinsufficiency causes developmental and expressive language delay indicating a phenotype distinct from Schinzel-Giedion syndrome

Abstract

SETBP1 expression was reduced in a patient with SETBP1 haploinsufficiency, indicating that the SETBP1 deletion phenotype is allele dose sensitive. In correlation with the exclusive deletion of SETBP1, this study delimits a milder phenotype distinct from SGS overlapping with the previously described phenotype of del(18)(q12.2q21.1) syndrome including global developmental, expressive language delay and distinctive facial features. These findings support the hypothesis that mutations in SETBP1 causing SGS may have a gain-of-function or a dominant-negative effect, whereas haploinsufficiency or loss-of-function mutations in SETBP1 cause a milder phenotype.

High resolution array in the clinical approach to chromosomal phenotypes

“…In 2 families we identified small deletions each comprising only one coding gene leading to candidate gene identification (Filges et al, 2011a(Filges et al, , 2011b. Patients 16a and 16b are brothers and show X-linked DD and ID due to a maternally transmitted 200 kb deletion including PTCHD1.…”

De novo microdeletion of 5q14.3 excluding MEF2C in a patient with infantile spasms, microcephaly, and agenesis of the corpus callosum

“…Expression level of glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) was used for the internal control. Obtained data were evaluated by the Delta Delta Ct method [Filges et al, 2011]. After evaluation, the expression ratio (patient versus normal control) was calculated in each of the three examinations and the averaged data of three examinations were shown in Supplemental eFigure S1 (See Supporting Information online).…”

“…Expression levels of MEF2C and CCNH were analyzed by real-time PCR method using SYBR Green system as described elsewhere [Filges et al, 2011]. Total RNA extracted from immortalized lymphoblasts from the present patient and a normal control individual were used for templates.…”

BCL11A frameshift mutation associated with dyspraxia and hypotonia affecting the fine, gross, oral, and speech motor systems

“…Most of these mutations have a global, unspecific impact on speech development. However, some have an effect on specific aspects of language such as FOXP2 (Morgan, Fisher, Scheffer, & Hildebrand, 2016; Reuter et al, 2017) or GRIN2A (Lai, Fisher, Hurst, Vargha‐Khadem, & Monaco, 2001; Myers & Scheffer, 2016; Turner et al, 2015) anomalies, which lead to childhood apraxia of speech, oral motor dyspraxia, and dysarthria, or SETBP1 encompassing 18q12.3 deletions which seems to impact expressive language, while preserving receptive language (Filges et al, 2011; Marseglia et al, 2012). …”