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S Savasta

Publications and source records attributed to S Savasta.

At least 19 recordsLinked to original sources
PubMed2001

Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.

Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.

Acanthosis Nigricans↗
PubMed2001

Symptomatic unilateral renal angiomyolipoma in a child with tuberous sclerosis.

We report a case of unilateral renal angiomyolipoma in a 10-year-old boy with tuberous sclerosis. The case is worthy of attention because the symptoms occurred at an early age and because the lesion was unilateral, the latter confirmed at 11-year follow-up. The presentation and treatment are discussed, and the pertinent literature is reviewed. The case demonstrates that it is of clinical importance to monitor renal involvement in children with tuberous sclerosis.

Angiomyolipoma↗
PubMed2001

Leigh disease: clinical, neuroradiologic, and biochemical study of three new cases with cytochrome c oxidase deficiency.

Three cases of Leigh disease are described. In all three, symptoms began in the first months of life, with muscle hypotonia, lactic acidosis, and psychomotor delay. The diagnosis was made on the basis of the clinical characteristics, biochemical abnormalities, and typical brain magnetic resonance imaging with symmetric lesions suggesting bilateral necrosis at the level of the basal ganglia and of the midbrain. Cytochrome c oxidase (complex IV of the mitochondrial respiratory chain) deficiency was demonstrated in muscle tissue in all patients and confirmed in skin fibroblasts in patient 3. A genetic heterogeneity was present in these patients since only one had a SURF-1 gene mutation. The clinical, biochemical, and neuroradiologic aspects are discussed. Finally, the finding of facial dysmorphisms in the cytochrome c oxidase deficiency observed in one of the described cases is of extreme interest; to our knowledge, this association has never been reported in the literature.

Acidosis, Lactic↗
PubMed1999

Genomic organization of the HSET locus and the possible association of HLA-linked genes with immotile cilia syndrome (ICS).

The kinesin-related protein (HSET) gene belongs to the kinesin superfamily, the members of which are involved in cellular transport processes. The HSET gene product was previously characterized by partial cDNA sequencing. The gene is located on the short arm of human Chromosome 6 (6p21.3), at the centromeric end of the major histocompatibility complex. Here, we report the genomic structure of the complete HSET gene together with its flanking loci. Sequence analysis of the 40 kilobase (kb) cosmid clone containing the HSET gene also revealed the presence of several new genes not related to the kinesin superfamily. These include a 60S ribosomal protein L35A-like pseudogene (rPL35A-like) on the telomeric side and a polycomb-like gene (PHF1), a copper tolerance-like gene (CUTA1) and the 5' part of the synaptic ras-GTPase-activating protein (SynGAP) gene centromeric of HSET. In addition, a complete 60S ribosomal protein L12-like (rPL12L) gene in intron 3 of the HSET gene was identified which appears to have an open reading frame. The possible involvement of the HSET gene and a beta-tubulin gene (TUBB) in the pathogenesis of immotile cilia syndrome (ICS) was studied by screening two unrelated ICS families with microtubular defects and suspected HLA linkage for mutations within the HSET gene and the TUBB gene. Four single base substitutions were detected in the HSET gene, and none in the TUBB gene. On the basis of these data, a role of the HSET and TUBB products in the pathogenesis of ICS in the two families is unlikely.

Amino Acid Sequence↗
PubMed1996

Cardiovascular reflex changes preceding episodes of vasovagal syncope in paediatric subjects.

1. The cardiovascular reflex changes preceding episodes of vasovagal syncope (VVS) in paediatric age were investigated in 12 subjects and in 20 controls, supine and upright, by spectral analysis of RR interval, respiration, systolic and diastolic blood pressure. 2. The sympatho-vagal control on the heart and blood pressure was assessed by the power of the low- (LF: index of sympathetic activity) and high-frequency oscillations (index of vagal activity to the heart). 3. In VVS group the supine blood pressure was lower than in controls and fell after tilt, while remained unchanged in controls. The blood pressure LF increased in control group during early and prolonged orthostasis, whereas in the VVS group the LF tended to decrease after early orthostasis and were not significantly greater than supine before VVS. 4. In the VVS group the sympathetic control of blood pressure appears reduced or ineffective, and progressively worsens before the VVS episode.

Adolescent↗
PubMed1996

Pyruvate dehydrogenase deficiency in a child responsive to thiamine treatment.

We report the clinical features in a 4-year-old child who was investigated for a suspected metabolic disorder but was subsequently diagnosed as having a pyruvate dehydrogenase deficiency. A muscle biopsy was performed and the data obtained suggested thiamine treatment which resulted in a regression of the clinical findings and a return to normal values of blood lactic and pyruvic acids. The interruption of thiamine supplementation after 1 year of treatment led to a prompt recurrence of the previous clinical and biochemical symptoms.

Biopsy↗
PubMed1996

Pulmonary changes in a man affected by von Recklinghausen's disease.

Lung involvement in von Recklinghausen's disease is very rare and only sporadic cases have been reported in the literature. We present the case of a man affected by neurofibromatosis type 1 (NF1). The man complained of shortness of breath of 3-4 years duration. Chest radiograph and computed tomographic (CT) scan showed the presence of severe bullous emphysema, with extensive widespread bulky subpleural bullae, involving mainly the upper lobes and apical segments of the lower lobes, bilaterally. Functional respiratory tests documented a picture of severe obstruction associated with marked alveolar hyperinflation (vital capacity (VC) 80% of predicted, forced expiratory volume in one second (FEV1) 49% pred, maximal mid-expiratory flow (MMEF) 22% pred, residual volume (RV) 151% pred). Capillary alveolar diffusion was also markedly altered (transfer factor of the lungs for carbon monoxide (TL,co) 41% pred). The eventual prospect of a lung transplant, never previously considered for this disease, has been advised by the thoracic surgeons. In the light of this possibility, multidisciplinary assessment and monitoring of respiratory function over time are indispensable, in order to identify the transplant window correctly.

Adolescent↗
PubMed1995

Recurrent chest pain as the presenting manifestation of spinal meningioma.

We report the case of a 9-year-old boy with a spinal cord meningioma whose only manifestations were recurrent episodes of chest pain lasting for 2 years. This case shows that spinal cord meningioma should be considered among the possible causative factors of chronic chest pain in childhood.

Chest Pain↗
PubMed1994

The motilin gene: subregional localisation, tissue expression, DNA polymorphisms and exclusion as a candidate gene for the HLA-associated immotile cilia syndrome.

The product of the human motilin gene (MLN) has an important role in regulating gastrointestinal motility. The precise chromosomal localisation and expression of this gene are still unresolved. Here, we report a detailed study assigning MLN to 6p21.3; MLN is tightly linked to the HLA-DQalpha locus. Moreover, MLN expression has been evaluated in a large series of tissues. Positive signals have been obtained for brain, bronchi and a gastrointestinal malignancy. Direct sequencing exon by exon of the codifying region, intron/exon boundaries and promoter has allowed the identification of three DNA polymorphisms, one of which corresponds to a common protein variant. The chromosomal localisation of MLN, and its expression in broncoepithelial cells suggests that this gene is involved in immotile-cilia syndrome (ICS) disease. Sequence and segregation analysis of the MLN gene carried out in two families, in which the disease locus was previously assigned to 6p21.3, exclude MLN as a candidate gene for the HLA-associated form of ICS.

Base Sequence↗
PubMed1993

Infantile mitochondria encephalomyopathies: report on 4 cases.

Four muscle biopsies from the quadriceps femoris muscle of children with symptoms suggesting mitochondrial encephalomyopathy were examined for morphological and biochemical differences. From a biochemical point of view, our patients showed a derangement of mitochondrial metabolism and in particular a marked deficit in the activity of cytochrome c oxidase. In all patients there was an abnormally high rise of lactate and pyruvic acid levels in blood before and after glucose loading. Results of morphological and enzyme histochemical studies showed smaller muscle fibre diameters than in normal children. Typical red ragged fibres and ultrastructural abnormalities in muscle mitochondria were present in 1 case only. Three patients showed focal changes in the distribution of some sarcoplasmic oxidative enzyme activities. The present findings suggest that the main metabolic disorder, pointed out by biochemical studies, is scarcely reflected by morphological and ultrastructural studies in the early stages of mitochondriopathies.

Biopsy↗
PubMed1993

Aplasia of the radial artery.

A 2-year-old girl with asymmetrical upper limbs and underdevelopment of the bones of the left forearm, wrist and hand with associated muscular and osteal hypoplasia is described. Doppler ultrasonography of the arterial trunks of the upper limb suggested a normal ulnar trunk in the left upper arm, an arterial vessel extending from the bend of the elbow to the distal third of the forearm, and the absence of any other arterial trunks in the radial region. Angiography confirmed that vascularization of the forearm was sustained by the ulnar artery, which supported the dorsal arch of the carpus and digital arteries arising from it. The interosseal artery was morphologically normal but there was aplasia of the radial artery. It is suggested that this malformation is the result of suppressed development of the vascular system of the left radial segment as other pathologies normally associated with the condition were absent.

Angiography↗
PubMed1993

[Vasovagal syncope].

The nature of most syncopal episodes, previously unknown, was recently elucidated by new diagnostic techniques such as the use of the tilt test. The vasovagal syncope can be clinically diagnosed by means of the tilt test. The transitory loss of consciousness during prolonged orthostasis is typically associated with sudden hypotension and bradycardia, which are commonly preceded by relative tachycardia and by premonitory symptoms such as pallor, nausea, asthenia, yawns, hyperventilation, mydriasis, humming, lasting several minutes. The nature of the vasovagal reflex is now better understood: in subjects with vasovagal syncope, during prolonged orthostasis, it was observed a fall in the venous return, inducing an increased sympathetic drive to the heart (with positive inotropic and chronotropic effect) and a lower ventricular filling. The powerful contraction around an almost empty cardiac chamber induces the activation of ventricular mechanoreceptors, and through a reflex mechanism, a sudden increase in the vagal and a sudden reduction in the sympathetic drive. These autonomic changes are responsible for a sudden hypotension and bradycardia. The discussion is still open about the origin of the reduced venous return: it probably originates from a redistribution in the blood volume, due to a venous pooling in the lower limbs or from a reduced muscle tone, because many subjects with vasovagal syncope are slender and with less developed muscle apparatus. Others suggest that a reduction in the sympathetic drive to the vessels, responsible for a progressive hypotension in the minutes preceding syncopal episodes, is the origin of the reduced venous return. In this review a diagnostic pattern for the assessment of the vasovagal syncope is suggested. The medical history, clinical examination, electro- and echocardiogram, chest x-ray identify two main groups of patients (with or without cardiopathy) who will follow different diagnostic protocols. The therapy of vasovagal syncope, which is based on beta-blockers, scopolamine, dysopiramide and plasma expanders, is reviewed.

Hemodynamics↗
PubMed1992

HLA haplotype segregation and ultrastructural study in familial immotile-cilia syndrome.

The immotile-cilia syndrome (ICS) is a congenital disorder characterized by dysmotility or even complete immotility of the cilia in the ciliated epithelia. The most frequent consequences include recurrent airway infections from early childhood. Neonatal asphyxia often occurs. Males are usually sterile, whereas females may be fertile or infertile. The disease is inherited as an autosomal recessive trait, but previous attempts to localize the ICS susceptibility gene have so far been unsuccessful. Here, we present the case of two sib pairs affected by ICS from two unrelated families. The electron microscopic investigation of nasal biopsies showed structural anomalies of the cilia, characterized by single microtubules or doublets, arranged randomly in the axoneme. Histocompatibility antigen (HLA)-genotyping of all family members revealed: 1) a significant association of ICS with the HLA-DR7; DQW2 haplotype, which is shared by all the affected sibs (P = 0.0099; RR = 25.94); 2) a possible linkage of the ICS susceptibility gene with HLA, both the affected sibs being HLA-identical, the healthy brother in family B being HLA-different (sib-pair analysis: P less than 0.001).

Child, Preschool↗