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Biomedical subjects

M Tartaglia

Publications and source records attributed to M Tartaglia.

At least 19 recordsLinked to original sources
PubMed1999

Fibroblast growth factor receptor mutational screening in newborns affected by metopic synostosis.

A number of craniosynostotic disorders have recently been ascribed to mutations in genes coding for the fibroblast growth factor receptors(FGFRs). The common feature of these FGFR-associated conditions is the unilateral or bilateral premature ossification of the coronal suture. One distinct craniosynostotic condition is trigonocephaly, which results from the premature fusion of the metopic suture. Trigonocephaly mostly occurs as isolated cranial defect; however, the premature closure of the metopic suture may represent a feature of more complex craniosynostotic conditions in which a progressive involvement of other cranial sutures with age is observed. The possible involvement of mutated FGFRs in trigonocephaly was investigated in nine newborns affected by isolated premature synostosis of the metopic suture. All except one of these cases carried no mutations in the FGFR1-3 domains indicated as hot spots for craniosynostosis-associated mutations. A T(978)C transition in the FGFR2 exon IIIa was found in a patient who had a phenotype that apparently fitted the trigonocephalic condition at birth, but showed additional facial anomalies, which worsened progressively with age towards a Crouzon-like profile. The present finding points out the importance, from both diagnostic and prognostic points of view, of early FGFR mutational screening in craniosynostotic conditions, even in forms that apparently do not involve closure of the coronal suture at birth.

Craniofacial Abnormalities↗
PubMed1999

Decreased proliferation and altered differentiation in osteoblasts from genetically and clinically distinct craniosynostotic disorders.

Craniosynostoses are a heterogeneous group of disorders characterized by premature fusion of cranial sutures. Mutations in fibroblast growth factor receptors (FGFRs) have been associated with a number of such conditions. Nevertheless, the cellular mechanism(s) involved remain unknown. We analyzed cell proliferation and differentiation in osteoblasts obtained from patients with three genetically and clinically distinct craniosynostoses: Pfeiffer syndrome carrying the FGFR2 C342R substitution, Apert syndrome with FGFR2 P253R change, and a nonsyndromic craniosynostosis without FGFR canonic mutations, as compared with control osteoblasts. Osteoblasts from craniosynostotic patients exhibited a lower proliferation rate than control osteoblasts. P253R and nonsyndromic craniosynostosis osteoblasts showed a marked differentiated phenotype, characterized by high alkaline phosphatase activity, increased mineralization and expression of noncollagenous matrix proteins, associated with high expression and activation of protein kinase Calpha and protein kinase Cepsilon isoenzymes. By contrast, the low proliferation rate of C342R osteoblasts was not associated with a differentiated phenotype. Although they showed higher alkaline phosphatase activity than control, C342R osteoblasts failed to mineralize and expressed low levels of osteopontin and osteonectin and high protein kinase Czeta levels. Stimulation of proliferation and inhibition of differentiation were observed in all cultures on FGF2 treatment. Our results suggest that an anticipated proliferative/differentiative switch, associated with alterations of the FGFR transduction pathways, could be the causative common feature in craniosynostosis and that mutations in distinct FGFR2 domains are associated with an in vitro heterogeneous differentiative phenotype.

Acrocephalosyndactylia↗
PubMed1998

Detection of bovine mitochondrial DNA in ruminant feeds: a molecular approach to test for the presence of bovine-derived materials.

A ban on ruminant-derived proteins in ruminant feeds has been introduced as a preventive measure to avoid the spread of bovine spongiform encephalopathy (BSE), as well as to minimize any potential risk of BSE transmission from bovines to humans. In the absence of commercially available efficient methods for identification of bovine-derived proteins in animal feeds, we developed a rapid and sensitive polymerase chain reaction (PCR)-based assay which allows detection and identification of a bovine-specific mitochondrial DNA sequence from feedstuffs. The amplified product encodes for the whole ATPase subunit 8 and the amino-terminal portion of the ATPase subunit 6 proteins, which are known to exhibit a relatively low degree of conservation among vertebrates. The specific amplification of such a bovine mitochondrial sequence from reference feedstuff samples was demonstrated by means of both direct sequencing and single-strand conformational analysis of the PCR product. Specificity was also confirmed by the absence of detectable homologous PCR product when using reference feedstuff samples lacking bovine-derived meat and bonemeals, or genomic DNA samples from vertebrates whose offals are commonly included in animal feeds. This method allows detection of the presence of bovine mitochondrial DNA in feedstuffs containing less than 0.125% of bovine-derived meat and bonemeals. Furthermore, it does not appear to be considerably affected by prolonged heat treatment. DpnII and SspI restriction endonuclease digestions of the unpurified PCR product may be used routinely to confirm the bovine origin of the amplified sequence. Since this method is specific, rapid, and sensitive, it could be successfully utilized as a routine control assay to evaluate the presence of bovine-derived meat and bonemeals in ruminant feeds.

Adenosine Triphosphatases↗
PubMed1997

Trp290Cys mutation in exon IIIa of the fibroblast growth factor receptor 2 (FGFR2) gene is associated with Pfeiffer syndrome.

Pfeiffer syndrome is a skeletal disorder characterized by craniosynostosis associated with foot and hand anomalies. Mutations in the genes encoding fibroblast growth factor receptors 1 and 2 (FGFR1 and FGFR2) have recently been implicated in the aetiology of such a syndrome, as well as of other craniosynostotic conditions. We now report a novel missense mutation, a G to C transversion at position 1049 (exon IIIa) of FGFR2, detected in a patient with severe Pfeiffer clinical features. The mutation results in the substitution of a cysteine for tryptophan-290 in the third immunoglobulin-like domain and affects both spliceoforms of FGFR2. Mutations causing replacement of tryptophan-290 have also been reported previously in Crouzon syndrome, a similar but clinically distinct craniosynostotic disorder. This finding confirms the involvement of mutations of FGFR2 exon IIIa in Pfeiffer syndrome, and emphasizes both the extensive heterogeneity of the FGFR2 mutations that result in the Pfeiffer phenotype and the perturbations caused by unpaired cysteine residues in receptor dimerization and transduction of the FGFs signal.

Acrocephalosyndactylia↗
PubMed1997

Jackson-Weiss syndrome: identification of two novel FGFR2 missense mutations shared with Crouzon and Pfeiffer craniosynostotic disorders.

Jackson-Weiss syndrome is a rare skeletal disorder characterized by craniosynostosis associated with foot malformations. This condition is inherited as an autosomal dominant trait with complete penetrance and wide phenotypic heterogeneity. Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have been recently identified as causes of this syndrome and of at least four other craniosynostotic disorders, namely the Apert, Beare-Stevenson cutis gyrata, Crouzon and Pfeiffer syndromes. We report two novel FGFR2 missense mutations associated with phenotypes consistent with Jackson-Weiss syndrome. Both nucleotide changes predict a serine for cysteine-342 substitution in the second half of the third immunoglobulin-like domain. The replacement of Cys342 with arginine has previously been reported in one of the three Jackson-Weiss cases investigated. Interestingly, both Cys342Ser and Cys342Arg substitutions have been found to be associated with the Crouzon and Pfeiffer phenotypes; a phenotypic heterogeneity, Crouzon vs Jackson-Weiss clinical features, has been also observed for Gln289Pro and Ala344Gly amino-acid changes. This finding indicates the genetic homogeneity of the "heterogeneous" Jackson-Weiss phenotype and a common molecular basis for these apparently "clinically distinct" craniosynostotic disorders.

Acrocephalosyndactylia↗
PubMed1995

Genetic heterogeneity among the Hindus and their relationships with the other "Caucasoid" populations: new data on Punjab-Haryana and Rajasthan Indian states.

The genetic structure of Rajasthan Hindus and Punjab-Haryana Hindus and Sikhs has been studied for ABO, RH, APOC2, C6, C7, F13A, F13B, HP, ORM1, ACP1, ADA, AK1, ESD, GLO1, PGD, PGM1 subtyping, and PGP. This is the first genetic survey on Hindus of Rajasthan. Furthermore, many of these markers have never been studied on Hindus before (APOC2, C6, C7, F13A, F13B, ORM1, PGP). These data, together with those previously available for Hindus, have been utilized to analyze the within-Hindus genetic heterogeneity by RST statistic and correspondence analysis. The genetic relationships of Hindus to other Causcasoid populations were also investigated. In the first analysis, two eastern states (Orissa and Andhra Pradesh) were found to be quite separate from each other and clearly distinct from the northwestern and western states. Out of the markers which could not be utilized in this analysis, PGM1 subtyping turned out to discriminate between the Dravidian-speaking and the Indo-Aryan-speaking Hindus. The second analysis shows a clear-cut separation of Hindus from Europeans, with Near Eastern and Middle Eastern populations genetically in an intermediate position.

Blood Group Antigens↗
PubMed1995

[Isolated oculomotor palsy disclosing multiple myeloma].

Two cases of oculomotor nerves involvement as uncommon initial manifestation of a parasellar extramedullary plasmacytoma are reported. The first patient presented with an isolated left VI cranial nerve palsy; the second one had an incomplete left III cranial nerve palsy. In both cases clinical investigation and computed tomography revealed an intracranial plasmacytoma associated with multiple myeloma. It is important to underline the difference between an intracranial extramedullary plasmacytoma and a plasmacytoma associated with multiple myeloma. In fact the absence of a general associated illness should show a most favourable course.

Abducens Nerve↗
PubMed1994

Genetic relationships among the Native American populations.

Red cell antigen data were used to investigate the genetic relationship among the Native American populations and their affinities with Siberian and Eastern Asian populations. Correspondence analysis showed a clear subdivision of all the Native American populations into three clear-cut clusters corresponding to the three linguistic families (identified by Greenberg)--Amerind, Na-Dene and Eskimo-Aleut. This result, as well as the close genetic resemblance between the Eskimos and the Asian populations, support the conclusion that the Americas were populated during at least three distinct and subsequent migration waves of people coming from Asia.

Alleles↗
PubMed1994

EcoRI, RsaI, and MspI RFLPs of the COL1A2 gene (type I collagen) in the Cayapa, a Native American population of Ecuador.

EcoRI, RsaI, and MspI RFLPs of the COL1A2 gene were analyzed, using the polymerase chain reaction technique, for the first time in a native American population: the Cayapa of Ecuador. These polymorphisms recently turned out to be good anthropological markers, both at the allele and at the haplotype frequency level. These data underline the well-known genetic affinity between the Cayapa and Asian populations. Moreover, our data on DNA polymorphisms agree with the indication of extremely low, if any, gene flow into the Cayapa gene pool from the neighboring black community, as already suggested not only by cultural data but also by protein polymorphisms.

Alleles↗
PubMed1994

Linkage disequilibrium at the human phosphoglucomutase 1 locus.

By considering the four common PGM1 alleles as haplotypes, that is, combinations of mutations at two polymorphic intragenic sites (1/2 and A/B), we investigated the levels of linkage disequilibrium in 142 human population samples. These groups showed considerable diversity in their disequilibrium (Drel) and heterogeneity. In all the populations the disequilibrium was found to be due to an excess of 1A and 2B haplotypes, although this direction is the opposite of that expected according to the proposed phylogeny of the system. Natural selection could be one of the major causes for such a disequilibrium direction.

Alleles↗
PubMed1994

[Traumatic internuclear ophthalmoplegia].

The authors report a case of traumatic internuclear ophthalmoplegia and discuss its pathophysiologic mechanism. Internuclear ophthalmoplegia due to head trauma is uncommon, though it may be more common than reported since signs and symptoms typically resolve over weeks to months, and in multiple trauma patients other serious injuries overshadow disturbances of eye movements. A lesion involving medial longitudinal fasciculus was found by magnetic resonance imaging in the early post-traumatic period; this lesion was not seen when routine X-ray computed tomography was performed at the time of injury, confirming that magnetic resonance scanning is definitely superior to computed tomography for evaluating internuclear ophthalmoplegia.

Aged↗
PubMed1994

Genetic characterization of the Cayapa Indians of Ecuador and their genetic relationships to other Native American populations.

One-hundred sixty-four Cayapa Indians living in the Esmeraldas Province (northwest Ecuador) were studied for several erythrocyte genetic markers (ACP1, ADA, AK1, CA2, ESD, GLO1, G6PD, PGD, PGM1 subtyping and thermostability, PGM2, SODA, and HB). The Cayapa show allele frequencies typical of those of South American Indians. The absence of the CA2*2, G6PD*A, G6PD*A-, HBB*S, and HBB*C alleles and the low PGM1*1A and PGM1*2A and high PGM1*1B allele frequencies indicate that very little (no more than 2%), if any, genetic admixture has occurred with the black community living in the same area. Correspondence analysis was used to study the genetic relationships between the Cayapa and other linguistically defined Amerind populations and between the Amerinds and the other two native American groups, the Na-Dene and Eskimo-Aleut. The results of this analysis, obtained on the basis of some erythrocyte and serum markers and some blood group systems, show (1) the close affinity between the Cayapa and other South American populations, (2) the absence in the Amerind group of a clear-cut correspondence between linguistic classification and genetic relatedness, and (3) the evident distinctiveness of the Amerinds from other native American people.

Adult↗
PubMed1991

A survey of six genetic markers on the populations of Punjab and Rajasthan (India).

190 Punjabis (Hindus and Sikhs) of Chandigarh and 152 Hindus of Jodhpur (Rajasthan) were examined for six genetic markers, four of which (APO C-II, C6, C7 and FXIIIA) were not studied before in Asiatic Indians. For APO C-II and C7 only the common phenotype was found in a total of 229 and 99 subjects, respectively. For the remaining four markers the two samples were pooled since the gene frequency estimates were not significantly different: FXIIIA*2 = 0.205 +/- 0.016; C6*B = 0.366 +/- 0.037; PGM1*2 = 0.247 +/- 0.017; PGD*C = 0.041 +/- 0.008. These data may contribute to evaluate the extent of the Mongoloid genetic admixture into the Caucasoid gene pool of the Punjab and Rajasthan Hindu population.

Apolipoprotein C-II↗