In conclusion, we describe a unique case with monoallelic FGFR3 and biallelic ALPL mutations leading to features of both hypochondroplasia and hypophosphatasia.
The haplotype of C-C-G-C-T-G-C-C-G [in the order of DOCK7rs1168013 (G>C), rs10889332 (C>T); PCSK9 rs615563 (G>A), rs7552841 (C>T), rs11206517 (T>G); and GALNT2 rs1997947 (G>A), rs2760537 (C>T), rs4846913 (C>A) and rs11122316 (G>A) SNPs] was associated with increased risk of HCH and HTG.
The haplotype of C-C-G-C-T-G-C-C-G [in the order of DOCK7 rs1168013 (G>C), rs10889332 (C>T); PCSK9 rs615563 (G>A), rs7552841 (C>T), rs11206517 (T>G); and GALNT2rs1997947 (G>A), rs2760537 (C>T), rs4846913 (C>A) and rs11122316 (G>A) SNPs] was associated with increased risk of HCH and HTG.
The haplotype of C-C-G-C-T-G-C-C-G [in the order of DOCK7 rs1168013 (G>C), rs10889332 (C>T); PCSK9rs615563 (G>A), rs7552841 (C>T), rs11206517 (T>G); and GALNT2 rs1997947 (G>A), rs2760537 (C>T), rs4846913 (C>A) and rs11122316 (G>A) SNPs] was associated with increased risk of HCH and HTG.
The ZNF259rs2075290, ZNF259rs964184 and BUD13 rs10790162 SNPs were significantly associated with serum lipid levels in both HCH and non-HCH populations (P < 0.008-0.001).
We investigated the effect of statins and statins plus ezetimibe in 65 FH heterozygotes carrying LDLR-defective or LDLR-negative mutations as well as the effect of ezetimibe monotherapy in 50 hypercholesterolemic (HCH) patients intolerant to statins.
Genetic analysis revealed two germline mutations, a seven base-pair deletion in exon 12 (G70313-703129del) in one allele of the retinoblastoma gene (RB1) and the N540K (C1620C > A) mutation in one allele of the fibroblast growth factor 3 (FGFR3) gene, a frequent mutation in hypochondroplasia.
Genotyping/haplotyping in the three-generation family with hypochondroplasia showed that FGFR1, FGFR2 and FGFR3 genes were not linked to the hypochondroplasia phenotype in this family, thus further confirming the genetic heterogeneity of hypochondroplasia.
Genotyping/haplotyping in the three-generation family with hypochondroplasia showed that FGFR1, FGFR2 and FGFR3 genes were not linked to the hypochondroplasia phenotype in this family, thus further confirming the genetic heterogeneity of hypochondroplasia.
Pilot studies of short-term growth hormone therapy in patients with achondroplasia and hypochondroplasia and nasal-osteocalcin therapy in osteogenesis imperfecta patients has been described, but the long-term effectiveness of these treatments remains to be determined.
Taking into account the genotypic and phenotypic variations in HCH, we conducted a study with these 58 patients and tested them for mutations in the fibroblast growth factor receptor 3 (FGFR3) and the short stature homeobox (SHOX) gene.
Studies of the families of the heterozygous affected children demonstrated strong linkage (lod score 3.311 at zero recombination) of the IGF-I gene locus at chromosome 12q23 to this subgroup of hypochondroplasia.
Some children who present with proportionate short stature and hypochondroplasia fail to increase their growth rate at puberty, although the growth spurt can be restored by GH therapy.
Pilot studies of short-term growth hormone therapy in patients with achondroplasia and hypochondroplasia and nasal-osteocalcin therapy in osteogenesis imperfecta patients has been described, but the long-term effectiveness of these treatments remains to be determined.
Early development of extensive acanthosis nigricans (AN) is a key feature in some patients who have hypochondroplasia (HCH) in association with FGFR3 mutations.
Recently, AN was reported in HCH with p.K650T mutation in FGFR3, and to date, there are only three reports, comprising 18 cases, describing AN harboring this specific gene mutation.