Publications (21)30.9 Total impact
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Article: Histone acetylation deficits in lymphoblastoid cell lines from patients with Rubinstein-Taybi syndrome.
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ABSTRACT: Rubinstein-Taybi syndrome (RSTS) is a congenital neurodevelopmental disorder defined by postnatal growth deficiency, characteristic skeletal abnormalities and mental retardation and caused by mutations in the genes encoding for the transcriptional co-activators with intrinsic lysine acetyltransferase (KAT) activity CBP and p300. Previous studies have shown that neuronal histone acetylation is reduced in mouse models of RSTS. The authors identified different mutations at the CREBBP locus and generated lymphoblastoid cell lines derived from nine patients with RSTS carrying distinct CREBBP mutations that illustrate different grades of the clinical severity in the spectrum of the syndrome. They next assessed whether histone acetylation levels were altered in these cell lines. The comparison of CREBBP-mutated RSTS cell lines with cell lines derived from patients with an unrelated mental retardation syndrome or healthy controls revealed significant deficits in histone acetylation, affecting primarily histone H2B and histone H2A. The most severe defects were observed in the lines carrying the whole deletion of the CREBBP gene and the truncating mutation, both leading to a haploinsufficiency state. Interestingly, this deficit was rescued by treatment with an inhibitor of histone deacetylases (HDACi). The authors' results extend to humans the seminal observations in RSTS mouse models and point to histone acetylation defects, mainly involving H2B and H2A, as relevant molecular markers of the disease.Journal of Medical Genetics 01/2012; 49(1):66-74. · 6.36 Impact Factor -
Article: Mutation spectrum of MLL2 in a cohort of Kabuki syndrome patients
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ABSTRACT: BACKGROUND: Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histone methyl transferase MLL2 gene have been identified as its underlying cause. METHODS: Genomic DNAs were extracted from 62 index patients clinically diagnosed as affected by Kabuki syndrome. Sanger sequencing was performed to analyze the whole coding region of the MLL2 gene including intron-exon junctions. The putative causal and possible functional effect of each nucleotide variant identified was estimated by in silico prediction tools. RESULTS: We identified 45 patients with MLL2 nucleotide variants. 38 out of the 42 variants were never described before. Consistently with previous reports, the majority are nonsense or frameshift mutations predicted to generate a truncated polypeptide. We also identified 3 indel, 7 missense and 3 splice site. CONCLUSIONS: This study emphasizes the relevance of mutational screening of the MLL2 gene among patients diagnosed with Kabuki syndrome. The identification of a large spectrum of MLL2 mutations possibly offers the opportunity to improve the actual knowledge on the clinical basis of this multiple congenital anomalies/mental retardation syndrome, design functional studies to understand the molecular mechanisms underlying this disease, establish genotype-phenotype correlations and improve clinical management.Orphanet J Rare Dis. 01/2011; 6:38. -
Article: Clinical score of 62 Italian patients with Cornelia de Lange syndrome and correlations with the presence and type of NIPBL mutation.
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ABSTRACT: Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder characterized by facial dysmorphisms, upper limb abnormalities, growth and cognitive retardation. About half of all patients with CdLS carry mutations in the NIPBL gene. The first Italian CdLS cohort involving 62 patients (including 4 related members) was screened for NIPBL mutations after a clinical evaluation using a quantitative score that integrates auxological, malformation and neurodevelopmental parameters. The patients were classified as having an overall 'severe', 'moderate' or 'mild' phenotype. NIPBL screening showed 26 mutations so classified: truncating (13), splice-site (8), missense (3), in-frame deletion (1) and regulatory (1). The truncating mutations were most frequently found in the patients with a high clinical score, whereas most of the splice-site and all missense mutations clustered in the low-medium score groups. The NIPBL-negative group included patients covering the entire clinical spectrum. The prevalence of a severe phenotype in the mutated group and a mild phenotype in the non-mutated group was statistically significant. In terms of the isolated clinical signs, the statistically significant differences between the mutation-positive and mutation-negative individuals were pre- and post-natal growth deficits, limb reduction, and delayed speech development. The proposed score seems to be a valuable means of prioritizing the patients with CdLS to undergo an NIPBL mutation test.Clinical Genetics 09/2007; 72(2):98-108. · 3.13 Impact Factor -
Article: Mutation analysis of the NSD1 gene in a group of 59 patients with congenital overgrowth.
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ABSTRACT: Sotos syndrome is characterized by pre- and post-natal overgrowth, typical craniofacial features, advanced bone age, and developmental delay. Some degree of phenotypic overlap exists with other overgrowth syndromes, in particular with Weaver syndrome. Sotos syndrome is caused by haploinsufficiency of the NSD1 (nuclear receptor SET domain containing gene 1) gene. Microdeletions involving the gene are the major cause of the syndrome in Japanese patients, whereas intragenic mutations are more frequent in non-Japanese patients. NSD1 aberrations have also been described in some patients diagnosed as Weaver syndrome. Some authors have suggested a certain degree of genotype-phenotype correlation, with a milder degree of overgrowth, a more severe mental retardation, and a higher frequency of congenital anomalies in microdeleted patients. Data on larger series are needed to confirm this suggestion. We report here on microdeletion and mutation analysis of NSD1 in 59 patients with congenital overgrowth. Fourteen novel mutations, two previously described and one microdeletion were identified. All patients with a NSD1 mutation had been clinically classified as "classical Sotos," although their phenotype analysis demonstrated that some major criteria, such as overgrowth and macrocephaly, could be absent. All patients with confirmed mutations shared the typical Sotos facial gestalt. A high frequency of congenital heart defects was present in patients with intragenic mutations, supporting the relevance of the NSD1 gene in the pathogenesis of this particular defect.American Journal of Medical Genetics Part A 05/2005; 134(3):247-53. · 2.39 Impact Factor -
Article: The Williams syndrome: an Italian collaborative study.
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ABSTRACT: Williams syndrome (WS) is a multiple congenital anomalies/mental retardation syndrome caused by a microdeletion on the long arm of chromoome 7 including the elastin gene. Possibly it is a contiguous gene syndrome with autosomal dominant transmission. Seventy-seven WS patients from 11 Italian Pediatric-Dysmorphology-Genetics Units were collected by means of a questionnaire designed to draw a comprehensive clinical picture, to define the frequency of different traits and associations thereof, to better understand the clinical evolution, to improve the prognosis and to ameliorate the follow-up. The most important signs for diagnosis, based on their relative frequencies, are: mental retardation with characteristic outgoing behaviour and hoarse voice; facial findings like stellate iris, periorbital fullness and thick lips; congenital heart disease. The frequency of the clinical signs reported in our patients are on the whole concordant with those found in the literature; the only significant differences concern low stature, hallus valgus, hypoplastic nails, joint contractures and ear infections. The multisystemic nature of this syndrome requires a coordinated and integrated approach in order to avoid fragmentary interventions.Minerva pediatrica 11/1996; 48(10):421-8. -
Article: Novel findings in a patient with Weaver or a Weaver-like syndrome.
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ABSTRACT: We report on a young male patient with an overgrowth syndrome, who had normal birth weight. He had a number of manifestations typical of the Weaver syndrome (WS), such as advanced bone age, peculiar craniofacial appearance, and camptodactyly. He also showed severe mental and speech retardation and demineralisation of the bones of the hands and feet. The latter can be considered as unreported manifestations of WS, or the patient could represent an example of a new WS-like syndrome.American Journal of Medical Genetics 06/1996; 63(2):378-81. -
Article: Malformation syndromes with kidney dysplasia.
Birth defects original article series 02/1996; 30(1):379-95. -
Article: A case of short-rib syndrome without polydactyly in a stillborn: a new type?
Birth defects original article series 02/1996; 30(1):95-101. -
Article: Dicentric chromosome Y associated with Leydig cell agenesis and sex reversal.
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ABSTRACT: The nature of a non-mosaic marker Y chromosome observed in a pseudohermaphrodite patient with Leydig cell agenesis was investigated by high-resolution chromosome analysis and molecular probes from the Y chromosome. Cytogenetically, the marker chromosome appeared to be an isodicentric, with breakage in Yq11.21. Double copies of all Yp-specific loci tested, including SRY, were present. The most distal Yq portion detected in patient DNA was DXS278-C, which maps to interval D in the chromosome Yq deletion map. Fragment DXS278-B, which maps to deletion interval E, was absent. The possible relationship between this cytogenetic abnormality and Leydig cell agenesis, a finding never reported in association with Y chromosome rearrangements, is discussed.Clinical Genetics 02/1995; 47(1):38-41. · 3.13 Impact Factor -
Article: Six additional cases of the KBG syndrome: clinical reports and outline of the diagnostic criteria.
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ABSTRACT: A diagnosis of KBG syndrome was made in six unrelated patients. They presented with slight mental retardation, macrodontia, and skeletal abnormalities. Microcephaly, short stature, facial anomalies, and syndactylies were also noted. The diagnostic criteria of the KBG syndrome are discussed.American Journal of Medical Genetics 10/1994; 52(3):302-7. -
Article: Prenatal diagnosis of femur-fibula-ulna complex by ultrasonography in a male fetus at 24 weeks of gestation.
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ABSTRACT: We present a case of ultrasonographic prenatal diagnosis at 24 weeks of femur-fibula-ulna (FFU) complex. To our knowledge, this is the first report of an early prenatal diagnosis of FFU.Prenatal Diagnosis 07/1994; 14(6):502-5. · 2.11 Impact Factor -
Article: Cerebro-facio-articular syndrome of Van Maldergem: confirmation of a new MR/MCA syndrome.
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ABSTRACT: Van Maldergem et al. (1992) described a new syndrome in an 11-year-old girl, characterized by: mental retardation, hypotonia, dysmorphic facies with telecanthus, epicanthus, broad flattened nose, large inverted W-shaped mouth, malformed ears, finger camptodactyly, and joint hyperlaxity. In this report we present a 5-year-old girl with very similar clinical findings. We confirm the existence of this condition as an independent clinical entity, and we propose that, based on the major clinical manifestations, it should be defined as "cerebro-facio-articular" syndrome.Clinical Genetics 04/1994; 45(3):140-4. · 3.13 Impact Factor -
Article: CFC syndrome: report on three additional cases.
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ABSTRACT: We describe three patients, originating from three different Italian localities, affected by the cardio-facio-cutaneous (CFC) syndrome. In addition to a varying degree of mental retardation, these patients present characteristics consisting of a peculiar face with bitemporal frontal constriction and other anomalies involving the eyes, nose, ears, hair, skin, and heart that are consistent with this diagnosis.American Journal of Medical Genetics 09/1989; 33(4):476-8. -
Article: Abnormal B.A.E.P. in a family with Moebius syndrome: evidence for supranuclear lesion.
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ABSTRACT: A family with Moebius syndrome is presented. Neurological lesions in the affected members are various: complete VI and VII cranial nerves palsy associated with mental retardation in the proband; left convergent strabismus and mental retardation in a brother of the proband and only mental retardation in a sister of the proband. The brainstem auditory evoked potentials (B.A.E.P.), investigated in the proband and his affected sister, are abnormal. The presence of the anomaly after the 3rd wave is consistent with a disfunction of the auditory tract at a supranuclear level. The mental deficiency and the supranuclear site of the acoustic lesion are an indication for a more general involvement of C.N.S. than cranial nerve nuclei alone. Karyotype and dermatoglyphics of the three affected subjects were normal. The authors hypothesized the same disorganogenetic factor acting very early (4th-6th week of gestational age) on the metamerization process of limb buds mesoderm and brainstem gray matter.Clinical Genetics 06/1984; 25(5):459-63. · 3.13 Impact Factor -
Article: Abnormal B.A.E.P. in a family with Moebius syndrome: evidence for supranuclear lesion
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ABSTRACT: A family with Moebius syndrome is presented. Neurological lesions in the affected members are various: complete VI and VII cranial nerves palsy associated with mental retardation in the proband; left convergent strabismus and mental retardation in a brother of the proband and only mental retardation in a sister of the proband. The brainstem auditory evoked potentials (B. A.E.P.), investigated in the proband and his affected sister, are abnormal. The presence of the anomaly after the 3rd wave is consistent with a disfunction of the auditory tract at a supranuclear level. The mental deficiency and the supranuclear site of the acoustic lesion are an indication for a more general involvement of C.N.S. than cranial nerve nuclei alone.Karyotype and dermatoglyphics of the three affected subjects were normal. The authors hypothesized the same disorganogenetic factor acting very early (4th-6th week of gestational age) on the metamerization process of limb buds mesoderm and brainstem gray matter.Clinical Genetics 04/1984; 25(5):459 - 463. · 3.13 Impact Factor -
Article: [Partial trisomy 10q24 leads to 10qter due to familial translocation (9;10) (p24;q24) recurring in 3 generations].
Minerva pediatrica 06/1983; 35(10):515-9. -
Article: t(21q21q)/r[t(21q21q)] mosaic in two unrelated patients with mild stigmata of Down's syndrome.
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ABSTRACT: Two cases of t(21q21q)/r[t(21q21q)] mosaic in unrelated infants, 17 and 14 months old respectively are reported. The proportion of cells with the ring chromosome was 45% in the former, 80% in the latter. Both cases had mild manifestations of the Down's syndrome. The origin of this unusual mosaicism as well as the significance of the difference in the proportions of the ring chromosome in the two have been discussed.Annales de Génétique 02/1982; 25(1):56-8. -
Article: [Aarskog's syndrome (facial-digital-genital syndrome). Study of a family (author's transl)].
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ABSTRACT: A case of Aarskog syndrome in a 6-years old boy is reported. The patient showed clinical pictures typical of the syndrome: characteristic dysmorphic facies, palpebral ptosis, brachyfalangism, abnormality of the scrotum. Minimal stigmata and clinodactyly of 5th finger were present in a sister. Isolated bilateral clinodactyly was found in other 4 members of the family. The significance of this sign in the context of the syndrome has been discussed. Unusual dermatoglyphic patterns were present in the proband, mother and sister.La Pediatria medica e chirurgica: Medical and surgical pediatrics 3(4):323-5. -
Article: [Poland-Moebius syndrome. Description of a new case].
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ABSTRACT: A new case of Poland-Moebius syndrome in a male is report and developmental field and developmental field defect is debate.La Pediatria medica e chirurgica: Medical and surgical pediatrics 8(1):111-2. -
Article: [Severe mental retardation and slight dysmorphism in a child with a bisatellite extrachromosome: inversion duplication (15)?].
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ABSTRACT: A de novo tetrasomy 15 has been reported, in a 6 years old child. The patient had severe mental retardation an minimal physical stigmata, consisting in slight skeletal and facial dismorphism. Cytogenetic analysis showed that extrachromosome, G-like long, was bisatellited and dicentric and was interpreted either as an inversion duplication 15 or as 15; G or D translocation.La Pediatria medica e chirurgica: Medical and surgical pediatrics 4(5):559-61.
Top co-authors
Top Journals
Institutions
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1996
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Università degli Studi di Torino
Torino, Piedmont, Italy
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1995–1996
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Università Cattolica del Sacro Cuore
- Faculty of Medicine and Surgery
Milano, Lombardy, Italy
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1994
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Istituto Nazionale di Genetica Molecolare
Milano, Lombardy, Italy
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