4 articles
DiGeorge syndrome, known also as 22q11.2 deletion syndrome, is a rare multisystemic disorder characterized by a wide range of clinical features and may include thymic aplasia and subsequent immunodeficiency, conotruncal cardiac anomalies, typical facial features, palatal abnormalities, and hypocalcemia due to hypoparathyroidism.
Data were collected for 10 patients genetically confirmed with DiGeorge syndrome at the Institute of Mother and Child. This included general information, laboratory results, and clinical features.
The mean age at diagnosis was 74.6 months (3 months – 28 years). Most cases were sporadic, with only 2 patients having a history of DGS (n=1), or close relatives with cardiac malformations (n=1). The most common symptoms that led to diagnosis were congenital heart defects (90%), and facial dysmorphism (90%). Common clinical features included recurrent infections (40%) and ENT disorders (20%). Weight was within normal percentiles for the entire group, but a delay in height growth was noted. Regarding the immunological characteristics: lymphopenia was recorded in 20% of patients, and thrombocytopenia in 2 patients.
Given the diverse array of symptoms associated with DiGeorge syndrome, physicians should be knowledgeable about both typical and less common characteristics of the syndrome to facilitate optimal treatment and potentially enable early diagnosis.
Congenital disorders of glycosylation (CDG) represent a group of rare diseases with multisystem involvement and exponential expansion, characterized by defects in the glycosylation process, which is essential for the proper functioning of proteins and lipids. These often manifest under the guise of other pathologies. The objective of the study was to diagnose CDG using Isoelectric Focusing of Transferrin (IEFT) in the Republic of Moldova and to identify diseases that mimic CDG.
Following medical-genetic consultations at the Institute of Mother and Child, 320 patients suspected for CDG were selected. History, clinical and paraclinical data were collected, and the proposed research questionnaire was completed. After signing the informed consent, the biological samples (serum, plasma, urine, DNA, DBS) were collected from all patients. Screening serum using the IEFT method was performed for 150 patients due to limited availability of reagents. For cases with negative CDG results, selective molecular-genetic tests such as MLPA, CGH-array, WES/WGS were performed.
Clinical and paraclinical examination of patients suspected CDG revealed multisystem involvement in 99.1% of cases, predominantly affecting the central nervous system in 92.2%. System and organ evaluation showed that, in addition to neurological damage there were skeletal (22.5%), renal (10.9%), ophthalmological (38.8%), muscular (22.5%), hepatic (20.9%), cardiac (40.6%), auditory (5.9%), pulmonary (3.8%), and gastrointestinal (29.4%) involvement. Analysis of 150 serum samples by IEFT method identified 3 positive cases for CDG. Molecular genetic testing revealed additional two CDG cases with negative IEFT and over 50 rare pathologies that manifest under the guise of CDG.
Clinical heterogeneity and disruptions in various biological pathways contribute to the complexity of CDG diagnosis. The clinical overlap of genetic diseases represents a considerable challenge for clinicians, as similar symptoms between different genetic conditions can lead to confusion and delay in identifying the disease.
Wilson’s disease (WD) is a rare genetic disease with autosomal recessive transmission, thus screening of all family members of newly diagnosed patients is recommended. Therefore, we aimed to analyze the proband’s family members to detect asymptomatic cases and early treatment initiation.
There were retrospectively evaluated 12 families, between 2008 - 2023. The Leipzig Scoring System was used to assess the diagnosis. Genetic testing was performed in all cases by the Sanger sequencing method, examining exons with a high and moderate frequency of mutations.
All patients were of Caucasian origin, and originally from Moldova. No patient reported consanguineous relationships. In 9 families, first-degree relatives were tested - parents and siblings, in the other 3 cases only their descendants were evaluated. In 6/12 cases: both parents were healthy carriers; in the other 3 families, one parent was a healthy carrier, but the other parent had not been tested. Among siblings, 4 healthy carriers and 2 healthy siblings were identified. 7 new family members with WD were identified in 5/12 families. 6 patients were asymptomatic, and 1 was symptomatic. The most frequent mutations detected were p.H1069Q and p.G1341D, both as compound heterozygous and homozygous recessive. A rare mutation has been detected.
Genetic counseling is important for the family of the patient with Wilson’s disease, as the evaluation of first-degree relatives is recommended by all international guidelines. First-degree relatives include the proband’s siblings, as well as the proband’s offspring and parents. It is also important to assess distant relatives, especially in more isolated areas. Although it is an autosomal recessive disorder, systemic family screening is recommended, as cases of paradoxical transmission are recorded. The c.2292C>T variant, identified in one patient, represents a rare mutation that, when occurring in combination with another pathogenic mutation or a homozygous state, can cause WD.
Family screening greatly influences identifying asymptomatic members with Wilson’s disease. Genetic testing is very important in differentiating healthy carriers from asymptomatic members, especially when deciding treatment tactics.
Spinal Muscular Atrophy (SMA) is a genetic disorder caused by the loss of the survival motor neuron (SMN1) gene in over 95% of cases. Additionally, mutations in genes associated with the SMA chromosomal region can influence disease progression. Aim: To analyze the status of the NAIP and GTF2H2 genes in correlation with SMA.
The study included 105 patients suspected for SMA of which 50 with confirmed with SMA and 55 without causative deletions, and 107 healthy, unrelated individuals. The molecular genetics methods used were mPCR, PCR-RFLP and MLPA.
From 105 patients, 50 were confirmed with SMA. In this group were identified in 8 patients (16%) with a homozygous deletion of exon 5 of the NAIP gene, 4 patients (8%) had a heterozygous status, and 2 (4%) had duplications. In the rest of the patients (55), in which deletions of SMN1 exon 7 were not identified, homozygous deletion of exon 5 of the NAIP gene was established in one patient (2%), 3 patients (5%) had duplications of exon 5 of the NAIP gene, and one patient had 5 copies of the NAIP gene. In the 107 healthy controls, one patient (1%) was identified with a deletion of exon 5 of the NAIP gene. None of the patients with combined deletions of SMN1 and NAIP had deletions in GTF2H2.
The frequency of deletions in the NAIP gene was found to be higher in the SMA patient group compared to the control group. Thus, a significant relationship was identified, the P value being <0.00001. The significance threshold was set at p<0.05. The genetic patterning of genes associated with SMA is an important aspect in the study of molecular pathophysiology and assessment of disease prognosis, especially in the approach to gene therapies.