Search PubMed⌕ Search

Biomedical subjects

A Orrico

Publications and source records attributed to A Orrico.

At least 19 recordsLinked to original sources
PubMed2007

Unusually severe expression of craniofacial features in Aarskog-Scott syndrome due to a novel truncating mutation of the FGD1 gene.

Aarskog-Scott syndrome (AAS) is a rare, clinically and genetically heterogeneous condition characterized by facial dysmorphic features, short stature, brachydactyly, and genital anomalies. The X-linked form is caused by mutations of the FGD1 gene. Although clinical manifestations and diagnostic criteria are well established, diagnosis is not simple, as the spectrum of phenotypical features may be extremely variable. Here, we report on the clinical and genetic characterization of a family in which molecular analyses revealed the inheritance of a novel truncating mutation of the FDG1 gene (c.945insC) in two affected brothers, with one of them displaying unusually severe craniofacial abnormalities. This previously unreported combination of anomalies might be due to the occurrence of two distinct disorders (AAS and hemifacial microsomia) or may represent an extension of the AAS phenotypic spectrum. Our findings highlight the phenotypic heterogeneity of AAS, supporting the opinion that the FGD1 mutations result in a broad spectrum of severity and, in some cases, may express a clinical appearance very different than typically described.

Adolescent↗
PubMed2003

Retinochoroidal atrophy in two adult patients with Angelman syndrome.

We describe a new ocular finding, retinochoroidal atrophy (RCA), associated with optic disk paleness in two adult patients with Angelman syndrome (AS) due to maternal 15q11-13 deletion. The ocular involvement described in children with AS consists iris and choroids hypopigmentation due to loss of function of one copy of P gene involved in maternal deletion. The loss of one copy of the same gene of paternal origin leads to a similar ocular phenotype as in Prader-Willi syndrome (PWS). However to our knowledge, RCA has never been described before in PWS, suggesting that other maternally expressed genes, particularly UBE3A, could be responsible for the retinal changes observed in the adult AS phenotype. Although, further investigations would be necessary to better understand the role of the UBE3A in the retina, the findings reported here should prompt a systematic ophthalmologic evaluation adult patients with AS in order to establish the real incidence of RCA and prevent further disability in these patients.

Adult↗
PubMed2002

A Rett syndrome MECP2 mutation that causes mental retardation in men.

OBJECTIVE: To characterize the clinical features of a new type of X-linked mental retardation associated with MECP2 mutation in the index family. BACKGROUND: MECP2 mutations, originally described in a high percentage of patients with classic Rett syndrome, were considered lethal in men. The authors recently described a novel A140V MECP2 missense mutation in an Italian family with X-linked semidominant mental retardation. METHODS: The neurologic features of six symptomatic relatives (two women and four men) carrying the mutation were compiled. Laboratory investigations included EEG, EMG, conduction velocity (CV) of peripheral nerves, brain MRI, and (1)H-MR spectroscopy. RESULTS: Mental retardation and signs of neurologic impairment were present in all the affected members, but more pronounced in men. Neurologic features included slowly progressive spastic paraparesis/pyramidal signs (6/6), distal atrophy of the legs (6/6), ataxia (2/6), and postural tremor of the hands (3/6). Speech was preserved (6/6) but was dysarthric in the oldest brothers (2/6). Mild dysmorphic features were present in all cases. CONCLUSION: The neurologic disorder associated with A140V MECP2 mutation is not necessarily lethal in men, but they are more severely affected than women of the same family.

Adult↗
PubMed2002

Mutations in the RYR1 gene in Italian patients at risk for malignant hyperthermia: evidence for a cluster of novel mutations in the C-terminal region.

Mutations in the ryanodine receptor type 1 (RYR1) gene are associated with Malignant Hyperthermia (MH) and Central Core Disease (CCD). We report here on the molecular analysis of the RYR1 gene in Italian families referred as potential cases of MH or in patients with CCD or multicore/minicore myopathy. Of a total of 20 individuals with mutations in the RYR1 gene, 14 were part of a group of 47 MH susceptible (MHS) patients, 4 of 34 individuals diagnosed as MH equivocal (MHE), and 2 were patients diagnosed with minicore myopathy and CCD, respectively. Mutations were found to segregate with the MHS or MHE phenotype within the families of the probands. A discordance between phenotype and genotype was observed in a family where a mutation detected in an MHS proband was also found in the father who had been diagnosed MH normal (MHN) at the IVCT. In addition to known mutations, seven novel mutations were found, five of which occurred in exons encoding the C-terminal region of RYR1. These results indicate that the C-terminal region of RYR1 represents an additional hot spot for mutations in patients with MH, similar to what has been reported for patients with CCD.

Amino Acid Sequence↗
PubMed2002

Septo-optic dysplasia with digital anomalies associated with maternal multidrug abuse during pregnancy.

We describe a 16-year-old female affected by septo-optic dysplasia (SOD) with digital anomalies as additional feature. This rare developmental anomaly of midline brain structures can result from different pathogenetical events, including mutations of the homeo box gene HESX1, recently suggested as the etiological cause at least in a subset of patients. The absence of mutational involvement of this gene in our patient led us to consider, in alternative terms of pathogenesis, the maternal multidrug abuse occurring during pregnancy. Our report, in accord with previous experimental evidences, points out that illicit drug use might have played a causative role in brain development anomalies, thus our patient could represent an additional case of birth defects caused by a prenatal toxic exposure. The neurologic abnormalities and the clinical history of the patient are extensively reviewed. The need to include the SOD phenotype amongst the possible teratogenic effects of multidrug abuse is evidenced.

Abnormalities, Drug-Induced↗
PubMed2001

Possible case of Pitt-Hopkins syndrome in sibs.

In this article, we describe two sibs, a brother and sister, with severe mental retardation and multiple congenital anomalies including "coarse" facial features, short stature, seizures, hypertrichosis, short great toes, and overbreathing. Comparison of these patients with previous reports suggests that they could represent the first familial cases of the Pitt-Hopkins syndrome. The recurrence in sibs within the same family supports autosomal recessive inheritance for the condition. Variable expression of the respiratory symptoms, which has not been reported earlier, is underlined.

Abnormalities, Multiple↗
PubMed2001

Additional case of Marden-Walker syndrome: support for the autosomal-recessive inheritance adn refinement of phenotype in a surviving patient.

In this report, we present a 14-year-old girl, born to consanguineous parents, who presented with severe mental retardation, hypotonia, short stature, and congenital joint contractures. The craniofacial features were scaphocephaly, thin/long and immobile face, marked hypoplasia of the midface, temporal narrowness, blepharophimosis, palpebral ptosis, and strabismus. The combination of such a distinctive craniofacial appearance and psychomotor retardation allows us to recognize a new case of the Marden-Walker syndrome. Our patient represents one of the rare cases in which consanguineous mating supports the autosomal-recessive pattern of inheritance of this condition. Furthermore, through refining the phenotype of a surviving patient, this report may contribute to a better recognition of this disorder in older affected children.

Adolescent↗
PubMed2000

MECP2 mutation in male patients with non-specific X-linked mental retardation.

In contrast to the preponderance of affected males in families with X-linked mental retardation, Rett syndrome (RTT) is a neurological disorder occurring almost exclusively in females. The near complete absence of affected males in RTT families has been explained by the lethal effect of an X-linked gene mutation in hemizygous affected males. We report here on a novel mutation (A140V) in the MECP2 gene detected in one female with mild mental retardation. In a family study, the A140V mutation was found to segregate in the affected daughter and in four adult sons with severe mental retardation. These results indicate that MECP2 mutations are not necessarily lethal in males and that they can be causative of non-specific X-linked mental retardation.

Adult↗
PubMed2000

A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog-Scott syndrome).

Aarskog-Scott Syndrome (AAS) is an X-linked disorder characterised by short stature and multiple facial, limb and genital abnormalities. A gene, FGD1, altered in a patient with AAS phenotype, has been identified and found to encode a protein with homology to Rho/Rac guanine nucleotide exchange factors (Rho/Rac GEF). However, since this original report on identification of a mutated FGD1 gene in an AAS patient, no additional mutations in the FGD1 gene have been described. We analysed 13 independent patients with clinical diagnosis of AAS. One patient presented a mutation that results in a nucleotide change in exon 10 of the FGD1 gene (G2559>A) substituting a Gln for Arg in position 610. The mutation was found to segregate with the AAS phenotype in affected males and carrier females in the family of this patient. Interestingly, Arg-610 is located within one of the two pleckstrin homology (PH) domains of the FGD1 gene and it corresponds to a highly conserved residue which has been involved in InsP binding in PH domains of other proteins. The same residue is often mutated in the Bruton's tyrosine kinase (Btk) gene in patients with an X-linked agammaglobulinemia. The Arg610Gln mutation represents the first case of a mutation in the PH domain of the FGD1 gene and additional evidence that mutations in PH domains can be associated to human diseases.

Abnormalities, Multiple↗
PubMed1999

Mutations in the glucose-6-phosphate transporter (G6PT) gene in patients with glycogen storage diseases type 1b and 1c.

Glycogen storage diseases type 1 (GSD 1) are a group of autosomal recessive disorders characterized by impairment of terminal steps of glycogenolysis and gluconeogenesis. Mutations of the glucose-6-phosphatase gene are responsible for the most frequent form of GSD 1, the subtype 1a, while mutations of the glucose-6-phosphate transporter gene (G6PT) have recently been shown to cause the non 1a forms of GSD, namely the 1b and 1c subtypes. Here, we report on the analysis by single-stranded conformation polymorphism (SSCP) and/or DNA sequencing of the exons of the G6PT in 14 patients diagnosed either as affected by the GSD 1b or 1c subtypes. Mutations in the G6PT gene were found in all patients. Four of the detected mutations were novel mutations, while the others were previously described. Our results confirm that the GSD 1b and 1c forms are due to mutations in the same gene, i.e. the G6PT gene. We also show that the same kind of mutation can be associated or not with evident clinical complications such as neutrophil impairment. Since no correlation between the type and position of the mutation and the severity of the disease was found, other unknown factors may cause the expression of symptoms, such as neutropenia, which dramatically influence the severity of the disease.

Antiporters↗
PubMed1999

Autosomal recessive syndrome of growth and mental retardation, seizures, retinal abnormalities, and osteodysplasia with similarity to the Gurrieri syndrome.

We report on two sibs, brother and sister, with a multiple congenital anomaly/mental retardation syndrome consisting of severe growth and mental retardation, seizures, retinal abnormalities, osteodysplasia, brachydactyly, prognathism, and dental malocclusion. These clinical findings were present in both patients and seem to be consistent with the phenotype of the Gurrieri syndrome. The new features described in these sibs could expand the clinical spectrum of the Gurrieri syndrome and confirm the existence of this rare autosomal recessive condition.

Adult↗
PubMed1998

Mosaicism for full mutation and normal-sized allele of the FMR1 gene: a new case.

The main mutation in fragile X patients is the expansion of the CGG repeat in the first exon of the FMR1 gene, associated with hypermethylation of the proximal CpG island. An increasing number of atypical cases have been reported showing the coexistence of full mutation and premutated or normal-sized alleles. These genotypes are more difficult to detect, and if a PCR strategy alone is adopted, they can be incorrectly identified. We report on a fragile X man with severe phenotype and mosaicism for full mutation and a (CGG)7 normal allele, the shortest fragment reported as yet in mosaics. This case of mosaicism, as other similar cases previously reported, suggests that the normal-length allele can derive from a deletion during the same early stage of development in which the full mutation expansion also arose.

Adult↗
PubMed1997

An additional case of craniodigital syndrome: variable expression of the Filippi syndrome?

We report on a boy with severe growth and mental retardation, syndactyly of toes and facial anomalies. This phenotype can easily be classified in the group of craniodigital syndromes, but it is difficult to make a more clearly defined diagnosis, based on other minor anomalies, because of the presence of overlapping features. On the basis of various pathognomic features, we conclude that our patient could be an additional case of Filippi syndrome. Moreover, newly recognised features in this patient may be due to variability in phenotypic expression.

Abnormalities, Multiple↗
PubMed1991

Differential effect of adenosine on DNA synthesis in lymphoid and myeloid cell lines.

In this report, the effects of adenosine on the promyelocytic cell line HL-60 and on T-lymphocytic clones are compared. According to previous reports, adenosine induces a dose-dependent inhibition of DNA synthesis in T-lymphocytes. Conversely, adenosine dose-dependently enhances DNA synthesis in HL-60 cells, as documented with [3H]thymidine uptake studies and flow cytometric cell-cycle analysis. Unlike its effect on lymphocytes, the adenosine effect on HL-60 cells does not seem to be mediated by receptor binding, but it appears to be correlated with an intracellular mechanism following active uptake. Despite the different effects exerted by adenosine on lymphocytes and myeloid cells, a purinergic pathway appears to be more generally involved in the regulation of some phases of cell growth.

Adenosine↗