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Distrofiile musculare Duchenne şi Becker (DMD/BMD) sunt boli musculare progresive legate de X determinate de mutaţii în gena distrofinei (DMD). Multiplex Ligation - Dependent Probe Amplification (MLPA) este o metodă simplă, necostisitoare şi precisă pentru diagnosticul molecular al mutaţiilor genei DMD. Ea identifică variaţiile numărului de copii în gena distrofinei, dar trebuie completată cu secvenţierea genei în cazul identificării deleţiilor/duplicaţiilor unui singur exon. Scopul acestui studiu a fost de a evalua eficienţa MLPA ca test de screening al mutaţiilor în gena DMD la indivizii afectaţi şi femeile purtătoare, dar şi de a aprecia frecvenţa diferitelor tipuri de mutaţii şi de a verifica valabilitatea “regulii cadrului de lectură. Am folosit MLPA pentru detectarea deleţiilor/ duplicaţiilor în gena DMD la 53 indivizi (30 băieţi afectaţi şi 23 rude asimptomatice de sex feminin) trimişi pentru evaluare şi sfat genetic datorită suspiciunii clinice de DMD/BMD. La băieţii afectaţi (21 DMD şi 9 BMD) MLPA a avut o rată de detecţie de 63,5% (53,5% deleţii şi 10% duplicaţii). Cel mai frecvent deletat exon a fost exonul 45 şi cea mai frecventă duplicaţie a implicat exonii 3-5, confirmând prezenţa celor două regiuni critice mutaţionale raportate în literatură. Mutaţiile detectate în studiul nostru au avut o localizare uşor diferită comparativ cu datele din literatură. Regula cadrului de lectură a fost valabilă în 84% din cazuri.

Dizabilitatea intelectuală (DI) este o afecțiune frecventă, cu consecințe majore pentru individ, familie și societate. Datorită heterogenității sale clinice și genetice, în aproximativ 50% din cazuri etiologia bolii nu poate fi stabilită. Scopul acestui studiu a fost evaluarea capacității de stabilire a diagnosticului etiologic la 369 pacienți cu DI sindromic și rezultat normal sau incert la cariotip folosind o combinație de kituri MLPA. Toţi pacienţii au fost investigaţi prin metoda MLPA, folosind fie kiturile SALSA MLPA P064 sau P096, dacă fenotipul a fost sugestiv pentru un sindrom cu microdeleţie (subgrupul A - 186 pacienți), fie kiturile subtelomerice P036 și P070, dacă fenotipul nu a fost sugestiv pentru un sindrom cu microdeleţie sau rezultatul la cariotipul standard a fost incert (subgrupul B - 183 pacienți). Rezultatele anormale detectate de aceste kituri au fost caracterizate folosind kiturile MLPA corespunzătoare de urmărire (Telomere Follow-up set, P029-A1, P250-B2, ME028-B1). În subgrupul A am identificat 25 de pacienți cu microdeleții (13,4%). Folosind kiturile de screening subtelomeric și de urmărire la subgrupul B am detectat rearanjări criptice în 7,5% din cazuri și am identificat originea materialului suplimentar observat la cariotipul standard la 10 din 11 pacienți. Sumarizând datele obţinute din cele două loturi, folosirea combinată a seturilor MLPA a dus la stabilirea diagnosticului la 10,6% (38/358) dintre pacienții cu cariotip normal. Folosirea seturilor MLPA de urmărire a permis atât confirmarea prezenţei anomaliei, cât şi determinarea dimensiunii ei, ceea ce a facilitat interpretarea semnificaţiei clinice a rearanjărilor. Pentru laboratoarele care nu au acces la tehnologiile bazate pe microarray, folosirea mai multor kituri MLPA reprezintă o strategie eficientă pentru stabilirea diagnosticului etiologic la pacienţii cu DI.

Atherogenic dyslipidemia plays a critical role in the development of metabolic syndrome (MetS), being one of its major components, along with central obesity, insulin resistance, and hypertension. In recent years, the development of molecular genetics techniques and extended analysis at the genome or exome level has led to important progress in the identification of genetic factors (heritability) involved in lipid metabolism disorders associated with MetS. In this review, we have proposed to present the current knowledge related to the genetic etiology of atherogenic dyslipidemia, but also possible challenges for future studies. Data from the literature provided by candidate gene-based association studies or extended studies, such as genome-wide association studies (GWAS) and whole exome sequencing (WES,) have revealed that atherogenic dyslipidemia presents a marked genetic heterogeneity (monogenic or complex, multifactorial). Despite sustained efforts, many of the genetic factors still remain unidentified (missing heritability). In the future, the identification of new genes and the molecular mechanisms by which they intervene in lipid disorders will allow the development of innovative therapies that act on specific targets. In addition, the use of polygenic risk scores (PRS) or specific biomarkers to identify individuals at increased risk of atherogenic dyslipidemia and/or other components of MetS will allow effective preventive measures and personalized therapy. [ABSTRACT FROM AUTHOR]

Hereditary gingival fibromatosis is a rare disease characterized by various degrees of attached gingival overgrowth. It can be isolated or be part of some syndromes, the isolated form being sporadic or familial with autosomal dominant pattern of transmission. Our patient is a female with moderate gingival enlargement firm on palpation and with normal color. Both mandible and maxilla are involved and have functional impairment (the speech and mastication affected). The onset of the disease was in childhood during the eruption of permanent dentition and the patient was treated by repeated gingivectomy procedures. The personal history rules out the use of medications involved in gingival enlargement. Family history was positive for gingival overgrowth consistent with dominant inheritance. The syndromes with gingival fibromatosis were excluded. The patient was surgically treated and the histological features are consistent with gingival fibromatosis. The complex management includes gingivectomy for functional improvement of speech and mastication. Also, it is important to identify the isolated form or the syndromic one in order to provide appropriate genetic counseling. [ABSTRACT FROM AUTHOR]

Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia, determined by RUNX2 gene mutation (located on 6p21.1) encoding the transcription factor CBFA1 which has a major role in regulation of bone differentiation. The major clinical features include the presence of wide-large fontanels at birth, short stature and other skeletal abnormalities (brachydactyly, pes planus, genu valgum, scoliosis). Patients often have recurrent respiratory infections and a normal intellect. The disease has a high penetrance and variable expressivity, some patients presenting subtle clinical signs of the disease. We present a patient, L. E., male, diagnosed with cleidocranial dysplasia at the age of 8 years. The history revealed a delayed closure of the anterior fontanel (2 years and 6 months); at the age of 5 years the patient has been diagnosed with pituitary dwarfism and rickets. Clinical examination revealed: short stature, craniofacial dysmorphism (frontal bossing, delayed tooth eruption, agenesis of premolars), sloping shoulders, pectus excavatum, brachydactyly, pes planus and hypoplastic nails feet. Chest X-ray and thorax CT scan revealed the presence of bilateral clavicular hypoplasia and cranial MRI scan revealed the presence of a pituitary hypoplasia, frontal sinus agenesis and hypoplasia of the maxillary sinus. Hand X-ray revealed a delayed bone age. The treatment was symptomatic involving growth hormone replacement therapy and orthodontic, orthopedic and pediatric care. In conclusion, we emphasize the importance of clinical and radiological examination to achieve early diagnosis, to establish an appropriate treatment and prevention of complications of the disease. [ABSTRACT FROM AUTHOR]

Esophageal atresia (EA) is defined as the absence of an esophageal segment and is often associated with tracheoesophageal fistula (TEF). The incidence of EA with/ without TEF is between 1:3,000 and 1: 4,000 newborns. Approximately 50%-70% of cases associate a major congenital anomaly (MCA). Commonly associated malformations are cardiovascular (15-40%), gastrointestinal (25-30%), genitourinary (20-25%) and musculoskeletal (10-15%). Usually, the MCA associated with EA represent the component of a specific plurimalformative syndrome, like VACTERL association and CHARGE syndrome. In 5 to 10% of cases we can detect chromosomal abnormalities (trisomy 21 or 18, microdeletion 22q11.2). We present two patients with EA/TEF and genetic conditions. Case1 - female, 4 days old. Clinical features - intrauterine growth retardation, facial dysmorphism: dolicocephaly, micrognathia, dysplastic ears; prominent calcaneus, EA, heart defect, kidney anomaly. The clinical suspicion of Edwards syndrome was confirmed by karyotype that showed a 47,XX,+18 chromosomal formula. Case 2 - female, 5 days old. Clinical features - EA with TEF, vertebral anomalies, anal atresia, bilateral thumb hypoplasia. This clinical association of MCA was concordant with VACTERL association. Management, prognosis and genetic counseling will be discussed. Our cases illustrate the need for careful genetic evaluation for EA/TEF, especially when these are associated with MCA. [ABSTRACT FROM AUTHOR]

Campomelic dysplasia (CD) is a very rare, sporadic, autosomal dominant syndrome. CD is characterized by an association of skeletal (bowed long bones, pelvis and chest abnormalities, eleven rib pairs) and extraskeletal abnormalities (facial dysmorphism, sex-reversal in boy and visceral malformations). We report a case of a 3 days old male diagnosed by CD. At birth, the boy displayed severe asphyxia and therefore needed intensive care. Physical examination revealed short stature, a craniofacial dysmorphism, cleft palate, muscle hypotonia, skeletal anomalies (chest hypoplasia, curved short upper and lower limbs, talipes equinovarus) cardiac malformations, normal male genitalia. The X-ray examination showed bell-shaped, narrow thoracic cage, hypoplastic scapulae, reduced cranial, pelvic, tibial and fibular ossification, absence of nasal and sternal ossification, cervical kyphosis, 11 pairs of ribs, flat and short vertebral bodies, short humerus with widened distal epiphysis, anterolateral femoral and tibial bowing and ankle valgus deformity. Dextrocardia was identified on X-ray examination and on echocardiography. Karyotype was 46,XY. The particularities of cases are campomelic dysplasia with dextrocardia, but without sex-reversal. [ABSTRACT FROM AUTHOR]

Unlabelled: Trisomy X (47,XXX) is a gonosomal aneuploidy characterized by the presence of an extra X chromosome in a female person. Usually the diagnosis is established made postnatally by chromosome analysis in patients with suggestive clinical signs. Clinical signs vary by age. In prepubertal patients have a growth retardation associated with uncharacteristic facial dysmorphism, mild mental retardation with behavioral disorders, plus clinical signs of ovarian dysgenesis, postpubertal., Aim: We analyzed retrospectively the genotype - phenotype correlations for a selected group of 36 patients diagnosed with trisomy X (homogeneous or mosaic) by cytogenetic methods (X chromatin and karyotype)., Material and Methods: Analysis of the clinical data of 36 patients diagnosed with trisomy X and correlation with the results of X chromatin and karyotype., Results: Clinical signs detected in patients with homogeneous trisomy X 47,XXX (22.22%), mosaic 46,XX/47,XXX (16.66%) or 47,XXX/48,XXXX (5.55%) were prepubertal, growth retardation associated with dysmorphic facial (upslanted palpebral fissure, epichantus, thin lips) and postpubertal, signs of ovarian dysgenesis (secondary amenorrhea, early menopause). The phenotype of patients with different gonosomal mosaic corresponding to Turner syndrome, incorporating a cell line with trisomy X (55.55%) was variable, correlated with the type of chromosomal abnormalities detected., Conclusions: The results of our study are similar to those obtained in other studies and emphasizes that phenotypic variability of patients with trisomy X feature makes it difficult to genotype - phenotype correlations.

Unlabelled: Velo-Cardio-Facial Syndrome (VCFS) is characterized by congenital heart defects (CHD), palatal abnormalities, facial dysmorphism, neonatal hypocalcemia, immune deficit, speech and learning disabilities. SVCF is caused by microdeletion 22q11.2. Microdeletion is detected by fluorescence in situ hybridization (FISH). The highly variable phenotype makes diagnosis and selection for FISH more difficult., Aim: To retrospectively analyze and compare the phenotype of children with a clinical diagnosis of VCFS with/without 22q11 deletion; to verify the validity of literature guidelines and to describe combinations of clinical features that should lead to molecular analysis., Material and Methods: The present study was performed in 21 patients with a clinical diagnosis of VCFS. Methaphase chromosome spreads were prepared from phytohaemagglutinin stimulated lymphocyte culture by standard methods before FISH. The patients were divided into two groups according to FISH test: positive and negative., Results: The features commonly noticed in FISH positive patients were: palatal abnormalities/hypernasal speech, learning disabilities, facial dysmorphism, tapered fingers (6/6), CHD (5/6) and recurrent infections (2/6). In FISH negative patients the following were found: learning disabilities, CHD (12/15); facial dysmorphism (10/15), family history of CHD (7/15), short stature (6/15), hypocalcemia, tapered fingers (5/15), recurrent infections (3/15) and palatal cleft (2/15). In both groups, Tobias and McDonald-McGinn guidelines were positive., Conclusions: VCFS has a highly variable phenotype. Our study suggests that 22q11.2 deletion analysis by FISH should be performed in patients who have at least 2 (newborn)/3 (child, adult) specific criteria: CHD, hypocalcemia, palatal abnormalities, facial dysmorphism, learning disabilities, digital anomalies, and immune deficit.