Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia.

We studied nine Italian families with a pure form of autosomal dominant spastic paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We observed marked intrafamilial variability in both age-at-onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55 years to healthy carriers of the mutation after age 70. Four of nine probands harboured SPG4 mutations, We identified three new SPG4 mutations, all predicting a loss-of-func-tion with apparently important consequences for spastin function. RT-PCR studies predict loss-of-function as a possible mechanism leading to spastin-related HSP. The current study expands the spectrum of allelic variants in SPG4, confirming their pathological significance in pure AD-HSP and suggesting implications for the presumed function of spastin

Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia.

We studied nine Italian families with a pure form of autosomal dominant spastic paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We observed marked intrafamilial variability in both age-at-onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55 years to healthy carriers of the mutation after age 70. Four of nine probands harboured SPG4 mutations, We identified three new SPG4 mutations, all predicting a loss-of-func-tion with apparently important consequences for spastin function. RT-PCR studies predict loss-of-function as a possible mechanism leading to spastin-related HSP. The current study expands the spectrum of allelic variants in SPG4, confirming their pathological significance in pure AD-HSP and suggesting implications for the presumed function of spastin

Mutual intercultural relations among immigrant and autochthonous youth in Italy. Testing the integration, multiculturalism, and contact hypotheses

Italy is increasingly becoming a culturally complex society. This poses numerous challenges for developmental and educational psychology, mainly in terms of how to encourage adequate levels of social harmony by promoting positive development of both immigrant and autochthonous youth. Within this perspective, the current paper presents the Italian findings of the Mutual Intercultural Relations in Plural Societies (MIRIPS) international project, postulating the centrality of three core hypotheses: integration, multiculturalism, and contact. Two studies were performed to investigate these hypotheses. Study 1 comprised 188 Tunisian adolescents aged 13-18 (51% F; M-age=15.94), while Study 2 included 282 Italian adolescents aged 13-18 ( 58% F; M-age=16.34). Data collection involved completion of the Italian version of the MIRIPS questionnaires, including security, contact, attitudes, acculturation, and well-being measures. In both studies, hypotheses were simultaneously tested by a SEM approach. The tested theoretical models fit the data well. For Tunisian adolescents, establishing contacts with Italian peers was associated with acculturation outcomes of integration (contact hypothesis), that, in turn, were related to higher well-being (integration hypothesis). Also, higher levels of perceived discrimination were related to acculturation outcomes of separation (multiculturalism hypothesis). For Italian adolescents, feelings of security were linked to higher multicultural ideology and tolerance ( multiculturalism hypothesis) as well as to higher contact with immigrants, that, in turn, were connected to lower segregationist attitudes (contact hypothesis). Moreover, higher levels of acculturation expectation of multiculturalism (the idea that non-dominant/immigrant groups should be integrated by both maintaining the original culture and adopting the dominant/hosting culture) were linked to higher self-esteem (integration hypothesis). The findings substantially supported the three core hypotheses and provided insights for decision-makers and practitioners to design effective social policies and educational programs to enhance the quality of intercultural relations among youth in Italy

Current insights into familial spastic paraparesis: new advances in an old disease

Hereditary spastic paraparesis (HSP) comprises a clinically and genetically heterogeneous group of disorders characterized by progressive spasticity and hyperreflexia of the lower limbs. The past few years have witnessed an exponential increase in knowledge of this disease and we can now list 19 loci mapped on the human genome and eight genes cloned. However, this wider knowledge of the molecular basis of HSP has had limited impact on clinical practice: the use of antispastic drugs and regular physiotherapy still remain crucial in the therapeutic management of patients. Nonetheless, the identification of new genes mutated in HSP furthers comprehension of the pathomechanisms involved and helps in genetic counseling, especially of asymptomatic individuals who request molecular analyses

EARLY-ONSET PROGRESSIVE ATAXIA ASSOCIATED WITH THE FIRST CACNA1A MUTATION IDENTIFIED WITHIN THE I-II LOOP.

Familial hemiplegic migraine type 1, spinocerebellar ataxia type 6 (SCA6) and episodic ataxia type 2 (EA2) are allelic disorders associated with mutations in the CACNAIA gene, which encodes the alpha 1 subunit of the P/Q-type calcium channel (Ca(V)2.1). SCA6 and EA2 share a number of clinical features, such as prominent cerebellar involvement and good response to acetazolamide therapy. However, while SCA6 develops as a late-onset, progressive ataxia, EA2 has an earlier, and episodic, onset. We report on two sisters with a heterogeneous clinical phenotype. The first developed progressive cerebellar ataxia after age 30, without noticeable episodes of vertigo or headache. A 1 year trial with acetazolamide did not produce significant results. The other reported episodes of vertigo, headache and gait imbalance since late childhood, with good response to acetazolamide, before developing moderate chronic cerebellar ataxia. Brain MRI showed cerebellar atrophy, especially in the vermis, in both patients. Direct sequencing of CACNAIA identified a heterozygous 1360G > A mutation in exon 11 resulting in the substitution of alanine for threonine at residue 454 (p.Ala454Thr). This is the first description of a change residing in the cytoplasmic I-II loop associated with a clinical phenotype. (c) 2007 Elsevier B.V. All rights reserved