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Rita Mingarelli

Publications and source records attributed to Rita Mingarelli.

At least 19 recordsLinked to original sources
PubMed2007

A novel patient with Cooks syndrome supports splitting from "classic" brachydactyly type B.

We report on a 2-year-old girl affected by an isolated form of brachydactyly type B (BDB)-like malformation of the limbs consistent with Cooks syndrome (CS). A literature review was carried out in an attempt to delineate the CS clinical spectrum and separate it from BDB. The two conditions can be differentiated on clinical, radiological, and genetic grounds. In particular, CS shows a characteristic pattern of ungueal and phalangeal anomalies. In the hands, all rays are involved to a similar extent with bulbous tips. The feet are generally more severely affected than the hands. Involvement of the nails appears to be a primary feature and not secondary to phalangeal hypo/aplasia. Also, radial and ulnar rays are similarly affected. The CS clinical spectrum is expanded to include ungueal tumor-like lesions, observed in the present patient.

Child, Preschool↗
PubMed2006

Antenatal presentation of the oculo-auriculo-vertebral spectrum (OAVS).

We describe a fetus with abnormal ultrasound (US) imaging at 20 weeks showing hydrocephalus and radial aplasia. Post-mortem examination followed pregnancy termination and confirmed the diagnosis of oculo-auriculo-vertebral spectrum (OAVS). To delineate the pattern of prenatal features in OAVS, we reviewed 20 published fetuses showing abnormal US and/or magnetic resonance imaging. Gestational age at diagnosis ranged from 14 to 34-35 weeks. Cephalic abnormalities were found in only 52.4% (i.e., micro/anophthalmia, ear anomalies, hemifacial microsomia, and facial cleft). CNS defects occurred in 47.6% (i.e., hydrocephalus, occipital encephalocele, cerebellar hemisphere/vermis hypoplasia, and lipoma of the corpus callosum), together with abnormal amniotic fluid volume (AFV), either poly- or oligohydramnios. Nineteen percent had congenital heart disease, mainly atrioventricular septal defect. Hydroureteronephrosis, radial aplasia, lung, and kidney agenesis were additional findings. Recurrent patterns of anomalies included multiple asymmetric facial lesions (i.e., hemifacial microsomia, ipsilateral micro/anophthalmia, malformed ear) and CNS (particularly hydrocephalus) plus AFV abnormalities. In addition, prognosis of prenatally detected OAVS patients resulted more severe than generally observed in this condition.

Adult↗
PubMed2006

Genetic testing in Italy, year 2004.

A comprehensive and long-range monitoring of genetic testing is ongoing in Italy starting from 1987. The data collected by the last survey of year 2004, on behalf of the Italian Society of Human Genetics, included the activities of 88 clinical centres and 160 cytogenetic and 183 molecular genetic laboratories, hosted by 256 structures. Only 42% of them fulfilled the requirements of current Italian legislation. Genetic tests included 283,601 cytogenetic analyses. There have been 120,238 invasive prenatal samplings, 84% of which were amniocenteses. A significant north-to-south decreasing gradient was evident for all activities. This study has also surveyed 190,610 molecular genetic tests. CFTR gene analysis accounted for 23% of prenatal and 29% of postnatal molecular tests. In total, 420 different genes have been investigated, 10 of which comprised three-quarters of the whole activity. More than 10% of molecular tests were performed on fetal samples, the analysis of CFTR, DMD, FMR1, FMR2, and GJB2 genes accounting for 83% of all prenatal tests. In years 1997-2004, the demand of cytogenetic tests has increased two-fold and that of molecular tests has increased four-fold. Only 16% of cytogenetic and 12.5% of molecular tests have been followed by genetic counselling. This survey highlights the need for a major basic intervention in the general organisation of genetic structures in Italy, which should be rationalised in accordance with the national guidelines, and the necessity of constant training of general practitioners and education of consumers to the appropriate use of genetic testing.

Connexin 26↗
PubMed2006

LEOPARD syndrome: clinical diagnosis in the first year of life.

LEOPARD syndrome (LS) is an autosomal dominant syndrome characterized by multiple lentigines and café-au-lait spots, electrocardiographic-conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, abnormalities of the genitalia in males, retardation of growth, and deafness. LS shares many features with Noonan syndrome (NS), in which lentigines and deafness are usually not present. Molecular studies have shown that LS and NS are allelic disorders, caused by different missense mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located at chromosome 12q22-qter. The clinical diagnosis of LS is generally difficult in the first months of life because the distinctive lentigines are generally not present at birth and develop during childhood. From January 2002 to December 2004, we suspected LS clinically in 10 patients admitted to our genetic counseling services in the first 12 months of life. A PTPN11 gene mutation was detected in 8/10 (80%) patients. In one patient without a PTPN11 mutation a subsequent clinical diagnosis of neurofibromatosis type 1 (NF1) was made, following the evaluation of the mother, who had previously undiagnosed classic NF1. The age of LS patients with PTPN11 mutation ranged between 1 and 11 months (mean age +/- SD 7.5 +/- 3.96 months). Review of the clinical characteristics of patients with LS confirmed by molecular study during the first year of life demonstrates that the diagnosis of LS in the first months of age can be clinically suspected in patients presenting with three main features, that is, characteristic facial features (100%), hypertrophic cardiomyopathy (HCM) (87%), and cafe-au-lait spots (75%). Characteristic facial features can be mild or severe, and consist of hypertelorism, downslanting palpebral fissures, ptosis, and dysmorphic ears. The clinical suspicion of LS may be confirmed by molecular screening for PTPN11 mutations. An early diagnosis of the disease is useful for the prospective care of associated medical problems and for precise genetic counseling.

DNA Mutational Analysis↗
PubMed2005

Majewski osteodysplastic primordial dwarfism type II (MOPD II) complicated by stroke: clinical report and review of cerebral vascular anomalies.

We report on a 2 9/12-year-old boy with disproportionate short stature, microcephaly, subtle craniofacial dysmorphisms, and generalized skeletal dysplasia, who developed a left hemiparesis. Brain neuroimaging disclosed a complex cerebral vascular anomaly (CVA) with stenosis of the right anterior cerebral artery and telangiectatic collateral vessels supplying the cerebral cortex, consistent with moyamoya disease. Based on clinical and skeletal features, a diagnosis of Majewski osteodysplastic primordial dwarfism type II (MOPD II) was established. Review of 16 published patients with CVA affected by either Seckel syndrome or MOPD II suggested that CVA is preferentially associated to the latter subtype affecting about 1/4 of the patients.

Abnormalities, Multiple↗
PubMed2005

A new observation of acro-cardio-facial syndrome substantiates interindividual clinical variability.

We report on a baby presenting with ectrodactyly, heart defects, and mild facial dysmorphisms, an association recognized as acro-cardio-facial syndrome (ACFS). Based on the first three observations, the acronym CCGE, cleft palate, cardiac defect, genital anomalies, and ectrodactyly had been proposed to embrace the most consistent features of this syndrome. A subsequent report and the present patient point to an obvious interindividual and intrafamilial variability of this autosomal recessive disorder in which ectrodactyly was the sole characteristic shared by all affected individuals.

Abnormalities, Multiple↗
PubMed2005

Novel EXT1 and EXT2 mutations identified by DHPLC in Italian patients with multiple osteochondromas.

We describe the results of an optimised DHPLC-based mutation screening of the EXT1 and EXT2 genes in Italian patients affected by multiple osteochondromas [MO; also referred to as hereditary multiple exostoses (HME) in the literature], using a multistep approach. We first analysed 36 unrelated probands for EXT1 mutations by DHPLC analysis and subsequent direct sequencing of all samples with abnormal elution profile. Negative cases were then screened for EXT2 mutations using the same approach. In patients who tested normal at DHPLC screening, all EXT1 and EXT2 exons and splice-site junctions were directly sequenced. In 7 informative families, we also performed a pre-screening linkage analysis to selectively focus the DHPLC testing on the EXT1 or EXT2 gene. We detected 31 MO-related mutations, of which 23 (74%) were novel. Seven polymorphisms were also found. Twenty-four mutations (77%) were found in EXT1 and 7 (23%) in EXT2. No disease-causing mutations were detected in five of 36 patients, with a mutation frequency of 86%. According with previous studies, most mutations (90%) are loss of function. Neither false positive nor false negative results were obtained. This multistep method can be considered a fast and reliable diagnostic strategy for the detection of EXT1/2 mutations, with excellent sensitivity and specificity.

Alternative Splicing↗
PubMed2004

KBG syndrome in a cohort of Italian patients.

KBG syndrome comprises a distinct facial phenotype, macrodontia, short stature, and skeletal anomalies. So far, it has been reported in 29 individuals. Recently, diagnostic criteria were outlined. Here, we describe eight new patients whose clinical and radiological findings fit the diagnostic criteria of KBG syndrome. While most patients were sporadic in occurrence, in two families the disorder was transmitted from mildly affected mothers to their affected children. The phenotype of KBG syndrome has been reviewed based on published and present patients. EEG anomalies with or without seizures, mixed hearing loss, palatal anomalies with secondary speech disorder, distinct age-related behavior, and cryptorchidism are possible additional characteristics. Less common manisfestations were posterior fossa malformations, eye defects, and congenital heart defects.

Abnormalities, Multiple↗
PubMed2004

Disomy of distal Xq in males: case report and overview.

A 46,XYq 8-year-old male was referred for microcephaly, growth, and mental retardation, hypotonia, genital hypoplasia, and dysmorphisms. FISH analysis showed that the rearranged Y chromosome originated from an unbalanced translocation of Xq27.3-qter onto the deleted Yq11.22. Analysis of reported patients with disomy of region distal to Xq26 suggests that this rare anomaly, associated with failure to dosage compensate X-linked genes that are normally inactivated, when present in two copies, is causing a quite distinct phenotype. This imbalance is the aberrant by product of the recombinogenic pairing of the distal pseudoautosomal Xq-Yq region at male meiosis.

Abnormalities, Multiple↗
PubMed2004

Ablepharon-macrostomia syndrome in a 46-year-old woman.

Ablepharon-macrostomia syndrome (AMS) is a rare condition reported to date in 13 patients worldwide. AMS is characterized by absent or short eyelids, absent eyebrows and eyelashes, macrostomia, and external ear abnormalities. Additional features include alopecia or sparse hair, hypoplastic malar region, redundant skin, rudimentary nipples, abnormal genitalia. While the AMS phenotype is well delineated in infants and children, clinical manifestations are rather poorly characterized in adulthood. Here, we report on an Italian woman who received a diagnosis of AMS at the age of 46 years after several surgical treatments. A clinical comparison between our patient and previously reported AMS cases aids in delineating the adult phenotype of AMS and further broadens the clinical spectrum of this condition.

Ear↗
PubMed2004

Fluorescence in situ hybridization analysis of allelic losses involving the long arm of chromosome 17 in NF1-associated neurofibromas.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant condition associated with germline mutations of the NF1 gene located at chromosome band 17q11.2. Molecular analysis of a number of NF1-specific tumors has shown the inactivation of both NF1 alleles during tumorigenesis, supporting the tumor suppressor hypothesis for the NF1 gene. Using interphase dual-color fluorescence in situ hybridization (FISH) technique on paraffin-embedded tissues, we studied 11 plexiform, 4 cutaneous, and 6 subcutaneous neurofibromas. Cytogenetic analysis was conducted using two probes, one specific for the NF1 region (RP11-229K15) and one for the centromeric region of chromosome 17 as control. No large somatic deletions were found. Only in one of the plexiform neurofibromas loss of a whole chromosome 17 was observed. If we assume that dual-color FISH analysis is sensitive enough to detect the majority of large somatic deletions present, then other mutational mechanisms affecting the NF1 gene are probably involved in neurofibroma formation, and other tumor suppressor genes may play an important role in NF1 tumorigenesis.

Adolescent↗
PubMed2004

A homozygous GJA1 gene mutation causes a Hallermann-Streiff/ODDD spectrum phenotype.

Oculodentodigital dysplasia (ODDD) and Hallermann-Streiff syndrome (HSS) share several clinical characteristics. However, while ODDD is a dominantly inherited disorder due to mutations in the connexin 43 gene GJA1, the inheritance pattern of the HSS syndrome is still debated. Overlapping phenotypes have been described. In one of such cases we found a homozygous change at the very conserved R76 codon (c.227G>A, p.R76H), the clinically normal parents being heterozigous carriers of the same mutation. A different base change at the same codon (p.R76S) leads to a complete dominant ODDD phenotype. A case of full-blown HSS phenotype was also analysed but GJA1 mutations were not found. GJA1 homozygous hypomorphic mutations can result in a phenotype in the HSS/ODDD spectrum.

Abnormalities, Multiple↗
PubMed2004

A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome.

Noonan (NS) and multiple lentigines/LEOPARD syndromes (LS) have proved to be associated with distinct PTPN11 mutations. Noonan-like/multiple giant cell lesion syndrome (NLS) is a rare disease, characterised by short stature, facial dysmorphisms, congenital heart defect (CHD) and central giant cell lesions. PTPN11 gene mutations have been reported in a single NLS family and two sporadic patients. Here we report a patient with a complex phenotype progressing throughout the years from NS at birth towards LS and NLS. PTPN11 gene analysis disclosed a novel missense mutation (Ala461Thr) in exon 12, affecting the consensus sequence of the SHP2-active site. This observation joins together NS and LS to NLS into a unique genetic defect, broadening the clinical and molecular spectrum of PTPN11-related disorders.

Adolescent↗
PubMed2003

NF1 gene analysis based on DHPLC.

The high mutation rate at the NF1 locus results in a wide range of molecular abnormalities. The majority of these mutations are private and rare, generating elevated allelic diversity with a restricted number of recurrent mutations. In this study, we have assessed the efficacy of denaturing high-performance liquid chromatography (DHPLC), for detecting mutation in the NF1 gene. DHPLC is a fast and highly sensitive technique based on the detection of heteroduplexes in PCR products by ion pair reverse-phase HPLC under partially denaturing conditions. We established theoretical conditions for DHPLC analysis of all coding exons and splice junctions of the NF1 gene using the WAVEmaker software version 4.1.40 and screened for mutations a panel of 40 unrelated NF1 patients (25 sporadic and 15 familial), genetically uncharacterized. Disruptive mutations were identified in 29 individuals with an overall mutation detection rate of 72.5%. The mutations included eight deletions (exons 4b, 7, 10a, 14, 26, and 31), one insertion (exon 8), nine nonsense mutation (exons 10a, 13, 23.1, 27a, 29, 31, and 36), six missense mutations (exons 15, 16, 17, 24, and 31), four splice errors (exons 11, 14, 36, and 40) and a complex rearrangement within exon 16. Eighteen (62%) of the identified disruptive mutations are novel. Seven unclassified and three previously reported polymorphisms were also detected. None of the missense mutations identified in this study were found after screening of 150 controls. Our results suggest that DHPLC provides an accurate method for the rapid identification of NF1 mutations.

Adult↗
PubMed2003

DiGeorge subtypes of nonsyndromic conotruncal defects: evidence against a major role of TBX1 gene.

The role of the 22q11 region genes, and among them TBX1, in nonsyndromic conotruncal defects (CTDs) is still unclear. Mice hemizygous at the Tbx1 locus show a remarkable incidence of heart outflow tract anomalies, of the same type commonly found in DiGeorge/Velo-cardio-facial syndrome (DGS/VCFS). Mutation analysis of the TBX1 gene in isolated, nonsyndromic CTDs has not demonstrated any functional pathogenetic variation so far. We screened the TBX1 gene in 41 patients affected by nonsyndromic CTDs of the DGS/VCFS subtype, principally "atypical" tetralogy of Fallot. Besides a few polymorphisms, we did not find any pathogenetic variation. These results do not support a major role of the TBX1 gene as responsible for human nonsyndromic CTDs.

Adolescent↗
PubMed2003

Recurrent triploidy of maternal origin.

Triploidy is the most frequent chromosome aberration in first trimester spontaneous abortions. In contrast to aneuploidies due to nondisjunction, increased maternal age is not a risk factor and the mechanism of triploidy remains poorly understood. To date, recurrence of triploidy of maternal origin has been described only in a few families suggesting some underlying genetic factors. Here, we report on a woman who underwent three consecutive triploid pregnancies, in two of which maternal origin of triploidy was proved by molecular analysis.

Abortion, Habitual↗