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KBG syndrome is a rare genetic disease characterized mainly by skeletal abnormalities, distinctive facial features, and intellectual disability. Heterozygous mutations in ANKRD11 gene, or deletion of 16q24.3 that includes ANKRD11 gene are the cause of KBG syndrome. We describe two patients presenting with short stature and partial facial features, whereas no intellectual disability or hearing loss was observed in them. Two ANKRD11 variants, c.4039_4041del (p. Lys1347del) and c.6427C > G (p. Leu2143Val), were identified in this study. Both of them were classified as variants of uncertain significance (VOUS) by ACMG/AMP guidelines and were inherited from their mothers. ANKRD11 could enhance the transactivation of p21 gene, which was identified to participate in chondrogenic differentiation. In this study, we demonstrated that the knockdown of ANKRD11 could reduce the p21‐promoter luciferase activities while re‐introduction of wild type ANKRD11, but not ANKRD11 variants (p. Lys1347del or p. Leu2143Val), could restore the p21 levels. Thus, our study report two loss‐of‐function ANKRD11 variants which might provide new insight on pathogenic mechanism that correlates ANKRD11 variants with the short stature phenotype of KBG syndrome. [ABSTRACT FROM AUTHOR]

Objective: To explore the value of amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) in evaluating the effectiveness of therapy with recombinant human growth hormone (rhGH) in patients with idiopathic short stature (ISS) and isolated growth hormone deficiency (IGHD). Methods: Forty-eight prepubertal children (IGHD = 25, ISS = 23) treated for at least 1 year with rhGH were included. Insulin growth factor-1 (IGF-I) and NTproCNP serum levels were measured before starting treatment and again 6 months later. Twelve months after starting treatment, all patients were assessed and annual growth velocity (GV), height standard deviation score (HTSDS), and gain HTSDS ( ΔHTSDS) were recorded. In the GHD group, positive relationships between GV and change of IGF-ISDS ( ΔIGF-ISDS ), GV and change of NTproCNP concentrations ( ΔNTproCNP) were found. GH peak value was also positively associated with IGF-ISDS and NTproCNP before therapy and ΔIGF-ISDS and ΔNTproCNP were positively associated. In the ISS group, GV was associated with only ΔNTproCNP. Conclusions: NTproCNP is a novel biomarker of growth as levels increase during growth-promoting treatment. Furthermore, IGF-I is also valuable in evaluating the efficacy of rhGH therapy in short stature patients. [ABSTRACT FROM AUTHOR]

Objective: [corrected] To investigate the mutation at the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) nucleotide 1138 site for identifying the major pathologic mechanism of achondroplasia (ACH) and to evaluate the efficacy of denaturing gradient gel electrophoresis(DGGE) method for screening the point mutations., Methods: The genomic DNA from 17 clinically diagnosed ACH patients where analysed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) with Sfc I and Msp I restriction endonucleases and by PCR-DGGE technique for screening., Results: G to A transition mutation at nucleotide 1138 was detected in 14/17 of the ACH patients as heterozygotes by PCR-RFLP with Sfc I digestion. No 1138 G to C transition was detected by Msp I digestion. All of the 14 samples with G to A mutation were also found to be positive for point mutation by PCR-DGGE. No mutation was detected in 3 negative samples by PCR-RFLP, implying that there was actually no point mutation in this amplified region., Conclusion: Nucleotide 1138 in transmembrane domain of FGFR3 gene is the hot point for mutation in ACH and hence its major pathologic cause. PCR-DGGE is a sensitive and reliable technique for point mutation screening, especially for the heterozygotes.