Development of a valid and reliable instrument for the assessment of quality of life in parents of children with clefts.

PURPOSE: Orofacial clefts are the most common congenital malformations that affect craniofacial structures. Studies show that they have a major influence on psychological development of the patient, and on their families. A review of the literature showed a lack of specific questionnaires for children and their parents. This study investigated the impact of orofacial clefts in children on the quality of life of their parents. In addition, the results of the treatment and the quality of work of the health team members involved in this process were evaluated. MATERIALS AND METHODS: For the purpose of this study, an original questionnaire was made to analyse the effect of orofacial clefts in children who had undergone surgery on the quality of life of 73 of their parents. The questionnaire consisted of 28 simple statements, which were evaluated with a 5-degree Likert scale (from 1-fully disagree to 5-fully agree), did not require any specific additional clarification, and were easy to complete. RESULTS: Analysis of areas of the questionnaire that applied to the parents, resulted in two subscales, parental social health and child social health, which had satisfactory Cronbach's coefficients (0.907 and 0.897, respectively). However, some issues had a relatively poor coefficient of internal consistency, which justified their expulsion from the final model of the parent questionnaire. CONCLUSION: The questionnaire developed for this study comprised two subscales concerned with the social health of parents/respondents and the social health of adolescents, as perceived by the parents. It was a valid and reliable instrument, and it showed satisfactory quality of life for parents of adolescents with clefts.

Genetic changes in the RNA components of RNase MRP and RNase P in Schmid metaphyseal chondrodysplasia.

BACKGROUND: The Schmid type of metaphyseal chondrodysplasia (MCDS) is generally due to mutations in COL10A1 encoding for type X collagen of cartilage. METHODS: We performed a study on the genes coding for the RNA components of RNase MRP (MRPR) and RNase P (H1RNA) among 20 patients with diagnosis of MCDS and no mutations in COL10A1. RESULTS: Two patients were found to be homozygous for a base substitution G for A at nucleotide 70 of RMRP, which is the major mutation causing cartilage-hair hypoplasia. No pathogenic mutations were detected in H1RNA. CONCLUSION: Cartilage-hair hypoplasia diagnosis should be considered in patients with metaphyseal chondrodysplasia even in the absence of any extra-skeletal manifestations if no mutation in COL10A1 can be found and the family history is compatible with autosomal recessive inheritance. Correct diagnosis is important for genetic counselling and for proper follow up of the patients.

Improvement of lipoprotein lipid composition in type II diabetic patients with concomitant hyperlipoproteinemia by acipimox treatment. Results of a multicenter trial.

OBJECTIVE: To study the tolerability and efficacy of acipimox on hyperlipidemia and diabetes compensation in patients with NIDDM under conditions of a routine clinical practice. RESEARCH DESIGN AND METHODS: We recruited 121 patients (60 men and 61 women) from 10 participating clinical centers. They were randomly divided into two groups and treated for 3 mo either with acipimox (250 mg three times a day) or placebo, using an open study design. RESULTS: Acipimox treatment led to a significant drop in fasting serum total triglyceride levels (by 28%) after 1 mo of drug administration. This decrease prevailed up to the end of the 3-mo study. Serum total cholesterol levels declined by 14%, and high-density lipoprotein tended to rise in acipimox-treated patients. These changes in lipid metabolism were not accompanied by any adverse effects of acipimox on glucose metabolism as judged by HbA1c measurements and the oral glucose tolerance test. Eight patients (out of 82 treated with acipimox) reported moderate adverse events of transient character, such as skin reactions and gastric disturbances. CONCLUSIONS: Acipimox seems to be a useful agent for treatment of diabetic dyslipidemia and does not deteriorate glycemic control.

Heterotopia of the mandibular third molar: a case report.

A rare finding of unilateral heterotopia of a mandibular third molar was most probably caused by primary and total dislocation of the tooth base. Other possible causative factors, such as a lack of space between the mandibular second molar and the mandibular ramus or a disproportion between the base and the direction of growth of the third molar, have been considered in similar cases reported in the literature.

Novel mutations affecting LRP5 splicing in patients with osteoporosis-pseudoglioma syndrome (OPPG).

Osteoporosis-pseudoglioma sydrome (OPPG) is an autosomal recessive disorder with early-onset severe osteoporosis and blindness, caused by biallelic loss-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. Heterozygous carriers exhibit a milder bone phenotype. Only a few splice mutations in LRP5 have been published. We present clinical and genetic data for four patients with novel LRP5 mutations, three of which affect splicing. Patients were evaluated clinically and by radiography and bone densitometry. Genetic screening of LRP5 was performed on the basis of the clinical diagnosis of OPPG. Splice aberrances were confirmed by cDNA sequencing or exon trapping. The effect of one splice mutation on LRP5 protein function was studied. A novel splice-site mutation c.1584+4A>T abolished the donor splice site of exon 7 and activated a cryptic splice site, which led to an in-frame insertion of 21 amino acids (p.E528_V529ins21). Functional studies revealed severely impaired signal transduction presumably caused by defective intracellular transport of the mutated receptor. Exon trapping was used on two samples to confirm that splice-site mutations c.4112-2A>G and c.1015+1G>T caused splicing-out of exons 20 and 5, respectively. One patient carried a homozygous deletion of exon 4 causing the loss of exons 4 and 5, as demonstrated by cDNA analysis. Our results broaden the spectrum of mutations in LRP5 and provide the first functional data on splice aberrations.

High-performance liquid chromatographic determination of humic acid in environmental samples at the nanogram level using fluorescence detection.

A high-performance liquid chromatographic method for the determination of humic acid in environmental samples is presented. The humic acid is chromatographed as its sodium or calcium complex, eluting as a single, sharp peak. Coral skeletal matter, sea water, river water, soils and plant matter were successfully analysed. The detection limit is 15 ng. The relative standard deviation for a coral skeletal sample is 1.9%. Unusual chromatographic properties such as the occurrence of peak broadening with increased concentration appear to be due to a slow change in the equilibrium composition of humic acid. In solution, fulvic acid showed similar properties to humic acid.

Mutations of the alpha2(V) chain of type V collagen impair matrix assembly and produce ehlers-danlos syndrome type I.

Ehlers-Danlos syndrome (EDS) is a heterogeneous connective tissue disorder that severely impairs the structure and function of the skin, joints, eyes and blood vessels. We have identified mutations of the COL5A2 gene, which encodes the alpha2(V) chain of type V collagen, in two unrelated patients with the severe type I form of EDS. The first proband was heterozygous for a 7 bp deletion that resulted in skipping of exon 27 while the second proband was heterozygous for a single nucleotide substitution that resulted in skipping of exon 28. Cultured dermal fibroblasts from both probands produced about equal amounts of the normal and mutant alpha2(V) mRNAs and protein chains. The dermis from the first proband contained a sparse collagen fibrillar network with great variability in collagen fibril sizes and shapes. The dermal collagens were also abnormally soluble. Bone cells from the first proband also produced about equal amounts of the normal and mutant alpha2(V) mRNAs. However, the collagen fibrillar architecture and collagen solubility of the bone matrix were normal. Our findings show that heterozygous mutations of the COL5A2 gene can produce the EDS type I phenotype. They also suggest that type V collagen plays a more important role in collagen fibrillogenesis of dermis than that of bone.

COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS.

We have identified haploinsufficiency of the COL5A1 gene that encodes the proalpha1(V) chain of type V collagen in the classical form of the Ehlers-Danlos syndrome (EDS), a heritable connective-tissue disorder that severely alters the collagen-fibrillar structure of the dermis, joints, eyes, and blood vessels. Eight of 28 probands with classical EDS who were heterozygous for expressed polymorphisms in COL5A1 showed complete or nearly complete loss of expression of one COL5A1 allele. Reduced levels of proalpha1(V) mRNA relative to the levels of another type V collagen mRNA, proalpha2(V), were also observed in the cultured fibroblasts from EDS probands. Products of the two COL5A1 alleles were approximately equal after the addition of cycloheximide to the fibroblast cultures. After harvesting of mRNAs from cycloheximide-treated cultured fibroblasts, heteroduplex analysis of overlapping reverse transcriptase-PCR segments spanning the complete proalpha1(V) cDNA showed anomalies in four of the eight probands that led to identification of causative mutations, and, in the remaining four probands, targeting of CGA-->TGA mutations in genomic DNA revealed a premature stop at codon in one of them. We estimate that approximately one-third of individuals with classical EDS have mutations of COL5A1 that result in haploinsufficiency. These findings indicate that the normal formation of the heterotypic collagen fibrils that contain types I, III, and V collagen requires the expression of both COL5A1 alleles.