PMC:4574214 / 10664-12991 JSONTXT

{"project":"2_test","denotations":[{"id":"26376624-25741868-10040322","span":{"begin":2181,"end":2182},"obj":"25741868"}],"text":"ARID1B mutations in non-syndromic patients with short stature\nWe sequenced the coding regions and intron-exon boundaries of ARID1B in 48 non-syndromic short stature Chinese patients. We detected four missense variants (Fig. 2). Variants c.2351C \u003e T and c.4727C \u003e T in patients D and E respectively were inherited from their fathers and the c.2351 variant was present in a sister of normal height as well. Variants c.4346G \u003e C and c.5998G \u003e T in patients F and G were not identified in either parent. Paternity test confirmed the biological relationship between the probands and their parents (data available in Additional file 3), thus these two missense variants are de novo changes in the probands. Provocative growth hormone (GH) testing with intravenous infusion of Arginine and oral administration of clonidine was performed in the patients, following routine procedures. Patient E, F and G exhibited partial growth hormone deficiency by provocative GH testing (5-7ng/ml).Patient D had a normal growth hormone level (15.272ng/ml). None of them had intellectual disability or language impairment. Thus they are all considered to have non-syndromic short stature. Detailed clinical information of the four patients is presented in Additional file 1.\nFig. 2 ARID1B Sanger sequencing data of four patients and their parents\nThe four missense variants were all predicted to be deleterious by SIFT, PolyPhen2 and Condel (Additional file 4). They were novel variants and absent from 494 Chinese controls, the NHLBI Exome Variant Server 6500 dataset (http://evs.gs.washington.edu/EVS/) and the ExAC database (http://exac.broadinstitute.org/).\nWe detected 8 novel variants predicted to be deleterious in 494 Chinese controls. There is a significant enrichment of novel deleterious missense variants detected in short stature patients when compared to the normal Chinese controls (p = 0.016 Fisher exact test). It is unclear if the inherited variants in Patients D and E are pathogenic given the lack of segregation with short stature in the family. Partial penetrance of these two inherited variants are possible. Based on the recently published guideline for variant interpretation [9], the two de novo variants are classified as likely pathogenic and the other two variants are of uncertain significance (see Additional file 4)."}