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Milano, Italy

Barozzi S.,University of Milan | Soi D.,University of Milan | Gagliardi C.,Neurorehabilitation Unit | Selicorni A.,University of Milan Bicocca | And 5 more authors.
Gait and Posture

Impaired control of balance has been described in Williams syndrome (WS). The aim of this study was to investigate balance function by means of clinical and instrumental tests in order to measure postural sway in people with WS in an objective way. 23 WS patients (11 males, 12 females, mean age 17.52 ± 8.33 years) and 23 healthy subjects (11 males, 12 females, mean age 17.74 ± 8.93 years) performed static posturography with eyes open and closed, on a firm surface and on foam pads. The WS patients had higher mean length, velocity and surface values than controls under all of the test conditions, and their length and surface values were significantly higher in the eyes open test. The cognitive abilities of the WS patients were not related to their stabilometric performance. The greatest differences between the WS patients and the controls were found mainly in the older subjects. WS patients are more unstable than healthy subjects of the same age, particularly when they use visual information to maintain their balance: i.e. under conditions of normal everyday life. Possible explanations may be the ophthalmologic problems and the visuospatial difficulties attributed to a neural processing abnormality involving the dorsal stream impairment model. The balance function of WS patients is different from that of normal developing subjects, especially after adolescence when postural control is generally complete. This suggests an atypical developmental trajectory. © 2012 Elsevier B.V. Source

Ciolfi A.,University of Rome La Sapienza | Caputo V.,University of Rome La Sapienza | Leoni C.,Catholic University of the Sacred Heart | Melis D.,University of Naples Federico II | And 4 more authors.
Journal of Medical Genetics

Background: Kaufman oculocerebrofacial syndrome (KOS) is a developmental disorder characterised by reduced growth, microcephaly, ocular anomalies (microcornea, strabismus, myopia, and pale optic disk), distinctive facial features (narrow palpebral fissures, telecanthus, sparse and laterally broad eyebrows, preauricular tags, and micrognathia), mental retardation, and generalised hypotonia. KOS is a rare, possibly underestimated condition, with fewer than 10 cases reported to date. Here we investigate the molecular cause underlying KOS. Methods: An exome sequencing approach was used on a single affected individual of an Italian consanguineous family coupled with mutation scanning using Sanger sequencing on a second unrelated subject with clinical features fitting the disorder. Results: Exome sequencing was able to identify homozygosity for a novel truncating mutation (c.556C>T, p.Arg186stop) in UBE3B, which encodes a widely expressed HECT (homologous to the E6- AP carboxyl terminus) domain E3 ubiquitin-protein ligase. Homozygosity for a different nonsense lesion affecting the gene (c.1166G>A, p.Trp389stop) was documented in the second affected subject, supporting the recessive mode of inheritance of the disorder. Mutation scanning of the entire UBE3B coding sequence on a selected cohort of subjects with features overlapping, in part, those recurring in KOS did not reveal disease-causing mutations, suggesting phenotypic homogeneity of UBE3B lesions. Discussion: Our data provide evidence that KOS is caused by UBE3B loss of function, and further demonstrate the impact of misregulation of protein ubiquitination on development and growth. The available clinical records, including those referring to four UBE3B mutation-positive subjects recently described as belonging to a previously unreported entity, which fits KOS, document the clinical homogeneity of this disorder. Source

Moncini S.,University of Milan | Bedeschi M.F.,UOD Genetica Medica | Castronovo P.,University of Milan | Crippa M.,CNR Institute of Molecular Genetics | And 5 more authors.
Meta Gene

In this report, we describe two adult brothers affected by moderate non-specific intellectual disability (ID). They showed minor facial anomalies, not clearly ascribable to any specific syndromic patterns, microcephaly, brachydactyly and broad toes. Both brothers presented seizures. Karyotype, subtelomeric and FMR1 analysis were normal in both cases. We performed array-CGH analysis that revealed no copy-number variations potentially associated with ID. Subsequent exome sequence analysis allowed the identification of the ATRX c.109C>T (p.R37X) mutation in both the affected brothers. Sanger sequencing confirmed the presence of the mutation in the brothers and showed that the mother is a healthy carrier. Mutations in the ATRX gene cause the X-linked alpha thalassemia/mental retardation (ATR-X) syndrome (MIM #. 301040), a severe clinical condition usually associated with profound ID, facial dysmorphism and alpha thalassemia. However, the syndrome is clinically heterogeneous and some mutations, including the c.109C>T, are associated with a broad phenotypic spectrum, with patients displaying a less severe phenotype with only mild-moderate ID. In the case presented here, exome sequencing provided an effective strategy to achieve the molecular diagnosis of ATR-X syndrome, which otherwise would have been difficult to consider due to the mild non-specific phenotype and the absence of a family history with typical severe cases. © 2013 The authors. Source

Bedeschi M.F.,UOD Genetica Medica | Bianchi V.,UOD Genetica Medica | Gentilin B.,UOD Genetica Medica | Colombo L.,Unit di Terapia Intensiva Neonatale | And 7 more authors.
Orphanet Journal of Rare Diseases

It is not unusual for patients with "rare" conditions, such as skeletal dysplasias, to remain undiagnosed until adulthood. In such cases, a pregnancy may unexpectedly reveal hidden problems and special needs. A 28 year old primigravida was referred to us at 17 weeks for counselling with an undiagnosed skeletal dysplasia with specific skeletal anomalies suggesting the collagen 2 disorder, spondyloperipheral dysplasia (SPD; MIM 156550). She was counselled about the probability of dominant inheritance and was offered a prenatal diagnosis by sonography. US examination at 17, 18 and 20 weeks revealed fetal macrocephaly, a narrow thorax, and shortening and bowing of long bones. The parents elected to continue the pregnancy. At birth the baby showed severe respiratory distress for four weeks which then resolved. Mutation analysis of both mother and child revealed a hitherto undescribed heterozygous nonsense mutation in the C-propeptide coding region of COL2A1 confirming the diagnosis of SPD while reinforcing the genotype-phenotype correlations between C-propeptide COL2A1 mutations and the SPD-Torrance spectrum. This case demonstrates the importance of a correct diagnosis even in adulthood, enabling individuals affected by rare conditions to be made aware about recurrence and pregnancy-associated risks, and potential complications in the newborn. © 2011 Bedeschi et al; licensee BioMed Central Ltd. Source

Baranello G.,UO Neurologia Dello Sviluppo | Cesaretti C.,UOD Genetica Medica | Zambonin F.,UO Neuropsichiatria dellInfanzia e dellAdolescenza | Casalone R.,SSD Genetica | And 4 more authors.
Journal of Child Neurology

Few cases of mosaicism involving a normal cell line and an unbalanced autosomal translocation have been reported so far. No cases of partial trisomy 13 and partial monosomy 8 mosaicism have been published. The authors report a new patient with partial trisomy 13 and partial monosomy 8 mosaicism due to an unbalanced translocation (13/8). A postzygotic mitotic exchange of nonhomologous chromatids followed by the loss of one of the translocated chromatids has been hypothesized as the potential underlying mechanism. Although a clear correlation of the clinical features of the patient with his chromosomal abnormality can be challenging, dysmorphic features, hyperactive behavior, moderate developmental delay, and tonic-clonic seizures can be interpreted as secondary to the particular genotype of the patient. These findings should be taken into account in the diagnostic process of patients presenting with multiple congenital anomalies and/or mental retardation conditions. © The Author(s) 2013. Source

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