Gene mutation analysis of X-linked hypophosphatemic rickets / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the frequency and type of PHEX gene mutations in children with X-linked hypophosphatemic rickets (XLH), the possible presence of mutational hot spots, and the relationship between genotype and clinical phenotype.</p><p><b>METHODS</b>Clinical data of 10 children with XLH was retrospectively reviewed. The relationship between gene mutation type and severity of XLH was evaluated.</p><p><b>RESULTS</b>PHEX gene mutations were detected in all 10 children with XLH, including 6 cases of missense mutation, 2 cases of splice site mutation, 1 case of frameshift mutation, and 1 case of nonsense mutation. Two new mutations, c.2048T>C and IVS14+1delAG, were found. The type of PHEX gene mutation was not associated with the degree of short stature and leg deformity (P=0.571 and 0.467), and the mutation site was also not associated with the degree of short stature and leg deformity (P=0.400 and 1.000).</p><p><b>CONCLUSIONS</b>Missense mutation is the most common type of PHEX gene mutation in children with XLH, and c.2048T>C and IVS14+1delAG are two new PHEX gene mutations. The type and site of PHEX gene mutation are not associated with the severity of XLH.</p>

Clinical analysis and genetic diagnosis of short-limb inherited short stature diseases in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical manifestations, bone X-ray findings and genetic analysis results of three short-limb inherited short stature diseases: achondroplasia (ACH), hypochondroplasia (HCH) and pseudoachondroplasia (PSACH).</p><p><b>METHODS</b>The clinical manifestations, bone X-ray findings, and genetic analysis results of 10 children with genetically confirmed short-limb inherited short stature diseases, including 4 cases of ACH 3 cases of HCH, and 3 cases of PSACH, were analyzed.</p><p><b>RESULTS</b>The 10 patients had a mean body height of -3.69±1.79 SD, a mean sitting height/standing height ratio of 0.65±0.03, and a mean finger spacing/body height ratio of 0.93±0.04. Four ACH cases and 3 PSACH cases showed typical bone X-ray findings; one HCH case showed a smaller sciatic notch, and another HCH case showed no widening of interpedicular distance. G380R mutation in FGFR3 gene was detected in 3 of 4 ACH cases, and Y278C mutation in the other ACH case, N540K mutation in FGFR3 gene was detected in 3 HCH cases, and heterozygous mutations in COMP gene were detected in 3 PSACH cases.</p><p><b>CONCLUSIONS</b>Children with ACH and PSACH have severer short stature and skeletal deformities than children with HCH, who have mild, atypical clinical manifestations. Bone X-ray and genetic analysis are helpful for the diagnosis and differential diagnosis of the three diseases. The mutational hotspots in two genes are involved in the three diseases, which is conducive to clinical genetic diagnosis.</p>