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Biomedical subjects

H Plauchu

Publications and source records attributed to H Plauchu.

105 records · Page 6Linked to original sources
PubMedDate not supplied

Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia.

Hypophosphatasia is an inherited disorder characterised by defective bone mineralisation and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. We report the characterisation of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 13 European families affected by perinatal, infantile or childhood hypophosphatasia. Eighteen distinct mutations were found, only three of which had been reported previously in North American and Japanese populations. Most of the 15 new mutations were missense mutations, but we also found two mutations affecting donor splice sites and a nonsense mutation. A missense mutation in the last codon of the putative signal peptide probably affects the final maturation of the protein. Despite extensive sequencing of the gene and its promotor region, only one mutation was identified in two cases, one of which was compatible with a possible dominant effect of certain mutations and the putative role of polymorphisms of the TNSALP gene. In 12 of the 13 tested families, genetic diagnosis was possible by characterisation of the mutations or by use of polymorphisms as genetic markers. Hypophosphatasia diagnosis was assigned in two families where clinical, laboratory and radiographic data were unclear and prenatal diagnosis was performed in one case. The results also show that severe hypophosphatasia is due to a very large spectrum of mutations in European populations with no prevalent mutation and that genetic diagnosis of the disease must be performed by extensive analysis of the gene.

Alkaline Phosphatase↗
PubMedDate not supplied

Mutation in the zonadhesin-like domain of alpha-tectorin associated with autosomal dominant non-syndromic hearing loss.

A gene responsible for autosomal dominant non-syndromic hearing impairment in two families (DFNA8 and DFNA12) has recently been identified as TECTA encoding alpha-tectorin, a major component of the tectorial membrane. In these families, missense mutations within the zona pellucida domain of alpha-tectorin were associated with stable severe mid-frequency hearing loss. The present study reports linkage to DFNA12 in a new family with autosomal dominant high frequency hearing loss progressing from mild to moderate severity. The candidate region refined to 3.8 cM still contained the TECTA gene. A missense mutation (C1619S) was identified in the zonadhesin-like domain. This mutation abolishes the first of the vicinal cysteines (1619Cys-Gly-Leu- 1622Cys) present in the D4 von Willebrand factor (vWf) type D repeat. These results further support the involvement of TECTA mutations in autosomal dominant hearing impairment, and suggest that vicinal cysteines are involved in tectorial membrane matrix assembly.

Extracellular Matrix Proteins↗
PubMedDate not supplied

Elastin gene deletions in Williams syndrome patients result in altered deposition of elastic fibers in skin and a subclinical dermal phenotype.

Williams syndrome (WS) is a complex developmental disorder with multisystem involvement known to be the result of a microdeletion in the q11.23 region of chromosome 7. This deletion involves several genes, including the elastin gene. Although elastic fibers are important constituents of skin, little is known about the skin phenotype in WS patients. We have therefore studied the skin of four WS patients in which we've shown the deletion of one copy of the elastin gene. Physical examination and indirect immunofluorescent microscopy of elastin did not detect any major phenotypic or morphologic changes in the skin. We were able, however, to show subtle textural changes in skin and, by electron microscopy, that the amorphous component of elastic fibers in WS patients was consistently reduced when compared to normal controls. These findings indicate that deletion of one copy of the elastin gene results in reduced deposition of elastin in dermal elastic fibers, an altered elastic fiber ultrastructure, and a subclinical dermal phenotype in the children and young adult patients analyzed in this study.

Adult↗
PubMedDate not supplied

An abnormal concentration of cases of Rendu-Osler disease in the Valserine valley of the French Jura: a genealogical and demographic study.

An important concentration of patients with Rendu-Osler disease occurs in the Valserine valley of the French Jura. A study of marriages shows that, in spite of its somewhat remote location, the valley cannot be considered an isolate, but that, on the contrary, exogamy is widely practised. Only 17.8% of the genes of inhabitants during the present century can be traced to the original population, but persons affected with the disease belong to a subgroup of the population which has lived in the villages for more than 10 generations. All the patients in 85 sibships are related. The smallest number of originator couples who lived at the beginning of the eighteenth century amounts to 16, the unique originator may therefore have lived approximately four generations earlier. However, as other patients who lived at the periphery of the Valserine valley do not appear to be related to any patients living in the valley, and because there has been considerable immigration into the valley, a number of hypotheses to explain the distribution of the disease in the region remain possible.

Consanguinity↗
PubMedDate not supplied

Familial extrahepatic biliary atresia.

Only a small number of cases with familial extrahepatic biliary atresia, suggesting a recessive autosomal inheritance, have been reported. However, the cases reported in twins are consistent with an acquired disease. Here the case of two brothers with familial atresia of the extrahepatic biliary system is studied. Diagnosis was confirmed by laparotomy and histologic study of biliary fibrous remnants. In the present cases parental consanguinity might suggest a recessive autosomal inheritance. However, clustering of cases in a family might also suggest a common exposure to responsible factors not so far identified.

Biliary Atresia↗