Papers by Maurizio Clementi
Ultrasound in Obstetrics and Gynecology, 2002
ABSTRACT We have evaluated the effectiveness of routine prenatal ultrasound screening in detectio... more ABSTRACT We have evaluated the effectiveness of routine prenatal ultrasound screening in detection of selected groups of major gastrointestinal malformations occurring among 690 123 pregnancies monitored from July 1st 1996 to December 31st 1998 in 19 European Congenital Malformation Registries. There were 243 cases of abdominal wall defects, 177 cases of diaphragmatic hernia and 386 cases of gastrointestinal atresia/stenosis. Only 57% of cases with diaphragmatic hernia and two thirds of cases of omphalocele compared to 95% of the fetuses with gastroschisis are currently being identified in an unselected population offered routine mid trimester ultrasound screening in europe. Among various cases of atresia/stenosis, the highest detection rate was recorded for duodenal (59%) and anorectal (32%) anomalies. Sensitivity of prenatal ultrasound clearly depends on the type of malformation and the presence of other structural anomalies or chromosomal aberrations. There is also significant variation in detection rates between different european regions reflecting policies, equipment and operators experience. The highest rates of elective top after prenatal ultrasound diagnosis were observed for omphalocele (50 or 36%), and gastroschisis (32 or 30%), and lowest for esophageal atresia (8%).
Human genetics, 2001
Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus... more Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus and photodysphoria, moderate to severe reduction of visual acuity, hypopigmentation of the retina, and the presence of macromelanosomes in the skin and eyes. We have pre- ...
J Hum Genet, 2010
The 621+3 A>G variant of the CFTR ... more The 621+3 A>G variant of the CFTR gene was initially detected in four Greek patients with a severe form of cystic fibrosis, and it is reported to impair CFTR mRNA splicing. We present three lines of evidence that argue against the pathogenicity of this variant. First, its allelic frequency in the Italian population was 0.4%. Even considering the lowest value in the confidence interval we would expect 10% of Italian CF patients to be heterozygotes for this variant, whereas it has been reported only in one patient (0.04% of Italian CF patients). Second, expression of the 621+3 A>G variant in HeLa cells using a hybrid minigene showed that 39.5+/-1.1% of transcripts were correctly spliced, indicating that its effects on mRNA splicing are similar to those of the CFTR intron 8 5T variant, associated with congenital bilateral absence of vas deferens (CBAVD), but not with CF. Third, we have identified an asymptomatic individual who harbored the 621+3 A>G variant in trans with the Q552X mutation. Because 621+3 A>G is often included in population-screening programs, this information is critical to provide adequate counseling to patients. Further work should be aimed at investigating whether this variant may have a role in CBAVD or atypical CF.
American Journal of Medical Genetics, Mar 12, 1999
Growth abnormalities such as macrocephaly and short stature have been described and are considere... more Growth abnormalities such as macrocephaly and short stature have been described and are considered a consistent finding in neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders in man. We present here a clinical study on the growth profile of a sample of NF1 patients collected through a population-based registry that covers three contiguous regions of North-East Italy (NEI-NF Registry). Auxometric traits of 528 NF1 patients have been measured with the aim of drawing growth charts for height, weight, and head circumference (OFC). Height velocity charts were based on a subset of 143 children who underwent multiple measurements. No differences in height were apparent between NF1 and normal subjects up to age 7 (girls) and 12 (boys) years; subsequently, the 50th centile of NF1 subjects tends to overlap with the 25th centile of normal subjects, and the 3rd centile is much lower in NF1 subjects than in normal subjects, mainly during adolescence. The negatively skewed distribution of height seems to indicate that height growth impairment affects only a proportion of NF1 subjects; height growth impairment does not seem related to disease severity. As for weight, our data suggest that slight overweight is a characteristic of adult NF1 subjects (mainly among males), independent of disease severity. Height growth velocity is normal during childhood for both sexes, whereas the pubertal spurt is slightly anticipated and reduced in NF1 boys but not in girls. Our data confirm previous observations that macrocrania affects most NF1 subjects; the shape of the head growth curve is similar in NF1 and normal girls, whereas NF1 boys present an OFC pubertal growth spurt much more pronounced and delayed than normal boys. The disproportion between OFC and height seems to be related to disease severity in boys but not in girls. Growth charts presented here can be useful in neurofibromatosis clinics for the identification of the effects of secondary growth disorders, for growth prognosis, and for the evaluation of the effects of a therapy such as GH therapy after radiotherapy for optic glioma. Am.
Ophthalmic Genetics, 1985
A condition is described which is characterized by microphthalmia and congenital anterior polar c... more A condition is described which is characterized by microphthalmia and congenital anterior polar cataract, transmitted in an autosomal dominant fashion.
Hum Genet, 1991
Summary The authors report the results of a genetic analysis performed in 34 neurofibromatosis ty... more Summary The authors report the results of a genetic analysis performed in 34 neurofibromatosis type 1 (NF1) Italian families using five loci tightly linked to NF1: D17S33, D17S82, D17S83, D17S37, and D17S36. A twopoint linkage analysis was performed with the LINKAGE and the CRI-MAP programs. The map of the region was contructed using the MAP90 program. Data from the present
Journal of Clinical and Experimental Neuropsychology, 2015
Decision-making (DM) abilities have been found to be impaired in anorexia nervosa (AN), but few d... more Decision-making (DM) abilities have been found to be impaired in anorexia nervosa (AN), but few data are available about the characteristics and correlates of this cognitive function. The aim of the present study was to provide data on DM functioning in AN using both veridical and adaptive paradigms. While in veridical DM tasks, the individual's ability to predict a true/false response is measured, adaptive DM is the ability to consider both internal and external demands in order to make a good choice, in the absence of a single true "correct" answer. The participants were 189 women, of whom 91 were eating-disordered patients with a lifetime diagnosis of anorexia nervosa, and 98 were healthy women. All the participants underwent clinical, neuropsychological, and genetic assessment. The cognitive evaluation included a set of neuropsychological tasks and two decision-making tests: The Iowa Gambling Task and the Cognitive Bias Task. Anorexia nervosa patients showed significantly poorer performances on both decision-making tasks than healthy women. The Cognitive Bias Task revealed that anorexia nervosa patients employed significantly more context-independent decision-making strategies, which were independent from diagnostic subtype, handedness, education, and psychopathology. In the whole sample (patients and controls), Cognitive Bias Task performance was independently predicted by lifetime anorexia nervosa diagnosis, body mass index at assessment, and 5-HTTLPR genotype. Patients displayed poor decision-making functioning in both veridical and adaptive situations. The difficulties detected in anorexia nervosa individuals may affect not only the ability to consider the future outcomes of their actions (leading to "myopia for the future"), but also the capacity to update and review one's own mindset according to new environmental stimuli.
American Journal of Medical Genetics, Aug 1, 1997
We have characterized a familial form of osteogenesis imperfecta (OI). Following the identificati... more We have characterized a familial form of osteogenesis imperfecta (OI). Following the identification by ultrasound of short limbs and multiple fractures in a fetus at 25 weeks of gestation, the family was referred with a provisional diagnosis of severe OI. We detected subtle clinical and radiological signs of OI in the father and in the paternal grandmother of the proposita, who had never received a diagnosis of OI. Linkage analysis indicated COL1A2 as the disease locus. Heteroduplex analysis of reverse transcription-polymerase chain reaction (RT-PCR) amplification products of pro alpha2(I) mRNA from an affected member and subsequent sequencing of the candidate region demonstrated the presence of normal transcripts and a minority of transcripts lacking exon 26 (54 bp) of COL1A2. Sequencing of PCR-amplified genomic DNA identified an A --> G transition in the moderately conserved +3 position of the IVS 26 donor splice site. The mutant pre-mRNA molecules were alternatively spliced, yielding both full-length and deleted transcripts that represented less than 30% of the total pro alpha2(I) mRNA. The biochemical data on type I collagen synthesized by dermal fibroblasts showed intracellular retention of the mutant protein; failure to detect the shortened alpha2(I) chains either in the medium or in the cell layer may be the consequence of their instability at physiological temperature. These observations justified the mild resulting phenotype.
Psychiatry Research: Neuroimaging, 2015
Anorexia nervosa (AN) is a disorder characterized by high levels of cognitive control and behavio... more Anorexia nervosa (AN) is a disorder characterized by high levels of cognitive control and behavioral perseveration. The present study aims at exploring inhibitory control abilities and their functional connectivity correlates in patients with AN. Inhibitory control - an executive function that allows the realization of adaptive behavior according to environmental contingencies - has been assessed by means of the Stop-Signal paradigm. The study involved 155 patients with lifetime AN and 102 healthy women. A subsample underwent resting-state functional magnetic resonance imaging and was genotyped for COMT and 5-HTTLPR polymorphisms. AN patients showed an impaired response inhibition and a disruption of the functional connectivity of the ventral attention circuit, a neural network implicated in behavioral response when a stimulus occurs unexpected. The 5-HTTLPR genotype appears to significantly interact with the functional connectivity of ventral attention network in explaining task performance in both patients and controls, suggesting a role of the serotoninergic system in mechanisms of response selection. The disruption of the ventral attention network in patients with AN suggests lower efficiency of bottom-up signal filtering, which might be involved in difficulties to adapt behavioral responses to environmental needs. Our findings deserve further research to confirm their scientific and therapeutic implications.
Amer J Med Genet, 2005
Percentile charts of neonrital length, weight, head circumference, and weightflength squared have... more Percentile charts of neonrital length, weight, head circumference, and weightflength squared have been constructed using data based on 688 consecutivc! newborn infants with Down Syndrome and 6,890 normal newborn infants (control grou?) registered in the congenital malformation registers of North-East Italy and the Emilia-Romagna Region. All percentiles of growth variables are lower in Down syndrome than in the control infants, except for the weightflengt h2 percentiles, suggesting that growth in Don syndrome is prenatally reduced; overweight begins after birth.
Investigative ophthalmology & visual science, 2015
To evaluate the feasibility of near-infrared (NIR) imaging acquisition in a large sample of conse... more To evaluate the feasibility of near-infrared (NIR) imaging acquisition in a large sample of consecutive pediatric patients with neurofibromatosis type 1 (NF1), to evaluate the diagnostic performance of NF1-related choroidal abnormalities as a diagnostic criterion of the disease, and to compare this criterion with other standard National Institutes of Health (NIH) diagnostic criteria. A total of 140 consecutive pediatric patients (0-16 years old) affected by NF1 (at least two diagnostic criteria), 59 suspected (a single diagnostic criterion), and 42 healthy subjects (no diagnostic criterion) were consecutively included. Each patient underwent genetic, dermatologic, and ophthalmologic examination to evaluate the presence/absence of each NIH diagnostic criterion. The presence of NF1-related choroidal abnormalities was investigated using NIR confocal ophthalmoscopy. Two masked operators assessed Lisch nodules and NF1-related choroidal abnormalities. Neurofibromatosis type 1-related chor...
Giornale italiano di nefrologia: organo ufficiale della Societa italiana di nefrologia
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder, w... more Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder, with a prevalence of 1:400 to 1:1000. ADPKD is genetically and clinically heterogeneous. In addition, significant intrafamilial renal disease variability is evident. The prevalence of ADPKD patients on renal replacement therapy in Italy has been reported to be 8.2%. In the dialysis population of Vicenza province (northeast Italy), in one area especially, ADPKD cases account for 13.4%. We hypothesize that this high frequency is related to a founder effect in this geographically isolated population. Since April 2007 we have studied the characteristics of ADPKD patients and the presence of haplotypes shared by several families. The clinical profile of patients in the Vicenza province is similar to that described in the literature but there is a high prevalence of ADPKD in several isolated areas. These areas are characterized by the presence of three distinct haplotypes, suggesting a strong lineage-specific gene.
Autoimmunity reviews
Autoimmune rheumatic diseases (ARD) are prevalent in women during their childbearing age. For the... more Autoimmune rheumatic diseases (ARD) are prevalent in women during their childbearing age. For their treatment, high doses of corticosteroid (CS) for long-term periods are often required, increasing the risk of bone loss. According to recent guidelines, bisphosphonates (BP) should be used as first line treatment to prevent CS induced osteoporosis. However, due to their long-term release from bone and their ability to cross the placenta, it has been suggested to avoid BP in women during their fertile years. BP seem to decrease foetus bone length in pregnant animals, but not in humans, at least, when they are administered at therapeutic dosage. BP are embryo toxic in animals when used at high dosage. In a systematic literature review, we found 58 women treated with BP close before or during pregnancy, showing no related congenital malformations. However, the Unit of Clinical and Epidemiological Genetics in University of Padova collected ten cases of women treated with BP during pregnan...
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease with variable rate of p... more Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease with variable rate of progression. It is associated with inter- and intra-familial variability. Neutrophil gelatinase-associated lipocalin (NGAL) has been implicated in pathological conditions and it is proposed as a biomarker for CKD progression. Our aim was to evaluate whether NGAL could be a good marker for progression of ADPKD, as we hypothesized. ADPKD patients with confirmed mutations (PKD1 n=33; PKD2 n=17) were enrolled and followed in a prospective study. Creatinine (sCr) and NGAL values were measured at baseline and on follow-up. Plasma NGAL was measured by Triage point of care test. CKD progression was defined as 15% decrease in eGFR from baseline to follow-up. Patients were divided into 2 groups based on median baseline NGAL and compared by the Kaplan-Meier curve. We enrolled 50 ADPKD pts (60%M age 41yrs); mean sCr 1.30.7mg/dl and median eGFR was 62 mL/min/1.73m2. NGAL values are inversely correlate...
American journal of medical genetics. Part A, Jan 21, 2015
Cassina M, Rigon C, Casarin A, Vicenzi V, Salviati L, Clementi M. 2015. FBXO28 is a critical gene... more Cassina M, Rigon C, Casarin A, Vicenzi V, Salviati L, Clementi M. 2015. FBXO28 is a critical gene of the 1q41q42 microdeletion syndrome.
Journal of Dermatological Science, 2015
Fig. 2. (A) Detail of the array-CGH analysis showing the 518 kb deletion at Xp22.31 (with proxima... more Fig. 2. (A) Detail of the array-CGH analysis showing the 518 kb deletion at Xp22.31 (with proximal breakpoint at 85,47,56,249 and distal breakpoint at 90,74,82,646). DNA sequence information refers to the public UCSC database [Human Genome Browser, February 2009, assembly hg19 (NCBI Build 37.1)]. (B) RTq-PCR analysis of KAL1 exons 2, 6, 14 from genomic DNA. Oligonucleotide sequences and reaction conditions are available upon request. To evaluate the DNA copy number, the results were normalized against the albumin gene. CtrF1 and CtrF2: normal female controls; CtrM: normal male control. The asterisk indicates that the amplification failed (because of the hemizygous deletion). (C) RTq-PCR analysis of STS transcript on cDNA obtained from RNA extracted from blood mononuclear cells of the patient, his mother and healthy controls. CtrF1 and CtrF2: normal female controls; CtrM: normal male control. Note that the STS gene escapes X inactivation and thus control healthy females display a twofold STS expression compared to healthy males. (D) Sequence analysis of STS exon 10 showing the c.1393A > G p.(Lys465Glu) mutation (arrows) present in the heterozygous state in the mother and in the hemizygous state in the patient. (E) Alignment of STS proteins in vertebrates, and of different human arylsulphatases (ARSA = arylsulphatase A, ARSD = arylsulphatase D, ARSE = arylsulphatase E) showing the conservation of lysine 465 and of glutamate 373. (F) Molecular modelling of the region surrounding lysine 465 showing the interaction of its terminal amino group with the terminal carboxyl group of glutamate 373, a residue flanking the active site pocket.
Genetics in medicine : official journal of the American College of Medical Genetics, 2015
European journal of dermatology : EJD, 2013
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Papers by Maurizio Clementi