Tricho-Dento-Osseous Syndrome: A Report of a Familial Cluster and a Literature Review

Tricho-dento-osseous syndrome (TDO), is a very rare, autosomal dominant genetic disorder, commonly characterized by curly hair at infancy, severe enamel hypomineralization and hypoplasia with taurodontism teeth, bone defects and other deformities. Other phenotypic features include flat fingernails and altered craniofacial morphology. A genetic linkage has been identified on chromosome 17q21 in the DLX3 gene. Treatment plan of TDO is to prevent problems such as sensitivity and dental attrition of the hypoplastic structure of the tooth, to promote the esthetics and encourage self-confidence of the patient. In this case report, we present a family with the proband father, and the two children siblings affected by the TDO syndrome. We describe clinical and radiological features, along with dental characteristics and genetic background. Management of TDO syndrome necessitates a multidisciplinary approach, appropriate documentation, and long-term follow up.

Systemic Sarcoidosis: Sociodemographic and Genetic Characteristics in a Tunisian Population

Background: Sarcoidosis is a multi-systemic granulomatosis of unknown cause, characterized by a clinical polymorphism. It results from interplay of environmental and genetic factors. Objective: The aim of our study was to describe sociodemographic and genetic characteristics in Tunisian patients with sarcoidosis. Methods: We conducted a retrospective study of patients with sarcoidosis followed in the internal medicine and neurology departments at the Military Hospital of Tunis. We collected epidemiological characteristics. Genetic study concerned only patients who accepted to participate. DNA extraction was performed from whole blood. HLA class II typing and gene mutation testing of the ACE gene were also performed. Results: Our study concerned 50 patients. The mediastino-pulmonary involvement was the most frequent (72.3%), followed by neurological involvement (58.5%), cutaneous involvement (50.8%) and ophthalmological involvement (40%). Genetic analysis showed a high frequency of the HLA DRB1 * 1501 allele (38%), DD genotype (30%) and D allele (54%) of the ACE gene. Treatment with corticosteroids was most often used 73.85%. The evolution was favorable in 13 cases (26.15%), and stable in 63% of cases. Conclusion: sociodemographic and genetic characteristic are variable from one ethnic to another. Advances in genotyping and statistical analysis are helping to elucidate the genetics of sarcoidosis.

Genetic Findings as the Potential Basis of Personalized Pharmacotherapy in Phelan-McDermid Syndrome

Phelan-McDermid syndrome (PMS) is a genetic disorder often characterized by autism or autistic-like behavior. Most cases are associated with haploinsufficiency of the SHANK3 gene resulting from deletion of the gene at 22q13.3 or from a pathogenic variant in the gene. Treatment of PMS often targets SHANK3, yet deletion size varies from < 50kb to > 9Mb, potentially encompassing dozens of genes and disrupting regulatory elements altering gene expression, inferring the potential for multiple therapeutic targets. Repurposed drugs have been used in clinical trials investigating therapies for PMS: insulin-like growth factor 1 (IGF-1) for its effect on social and aberrant behaviors, intranasal insulin for improvements in cognitive and social ability, and lithium for reversing regression and stabilizing behavior. The pharmacogenomics of PMS is complicated by the CYP2D6 enzyme which metabolizes antidepressants and antipsychotics often used for treatment. The gene coding for CYP2D6 maps to 22q13.2 and is lost in individuals with deletions larger than 8Mb. Because PMS has diverse neurological and medical symptoms, many concurrent medications may be prescribed, increasing the risk for adverse drug reactions. At present, there is no single best treatment for PMS. Approaches to therapy are necessarily complex and must target variable behavioral and physical symptoms of PMS.

Role of Dot1L and H3K79 methylation in regulating somatic hypermutation of immunoglobulin genes

Somatic hypermutation (SHM) and class-switch recombination (CSR) of the immunoglobulin (Ig) genes allow B cells to make antibodies that protect us against a wide variety of pathogens. SHM is mediated by activation-induced deaminase (AID), occurs at a million times higher frequency than other mutations in the mammalian genome, and is largely restricted to the variable (V) and switch (S) regions of Ig genes. Using the Ramos human Burkitt’s lymphoma cell line, we find that H3K79me2/3 and its methyltransferase Dot1L are more abundant on the V region than on the constant (C) region, which does not undergo mutation. In primary naïve mouse B cells examined ex vivo, the H3K79me2/3 modification appears constitutively in the donor Sμ and is inducible in the recipient Sγ1 upon CSR stimulation. Knockout and inhibition of Dot1L in Ramos cells significantly reduces V region mutation and the abundance of H3K79me2/3 on the V region and is associated with a decrease of polymerase II (Pol II) and its S2 phosphorylated form at the IgH locus. Knockout of Dot1L also decreases the abundance of BRD4 and CDK9 (a subunit of the P-TEFb complex) on the V region, and this is accompanied by decreased nascent transcripts throughout the IgH gene. Treatment with JQ1 (inhibitor of BRD4) or DRB (inhibitor of CDK9) decreases SHM and the abundance of Pol II S2P at the IgH locus. Since all these factors play a role in transcription elongation, our studies reinforce the idea that the chromatin context and dynamics of transcription are critical for SHM.

Systemic Sarcoidosis: Sociodemographic and Genetic Characteristics in a Tunisian Population

Sarcoidosis is a multi-systemic granulomatosis of unknown cause, characterized by a clinical polymorphism. It results from interplay of environmental and genetic factors. The aim of our study was to describe sociodemographic and genetic characteristics in Tunisian patients with sarcoidosis. We conducted a retrorospective study of patients with sarcoidosis followed in the internal medicine and neurology departments at the Military Hospital of Tunis. We collected epidemiological characteristics. Genetic study concerned only patients who accepted to participate. DNA extraction was performed from whole blood. HLA class II typing and gene mutation testing of the ACE gene were also performed. Our study concerned 50 patients. The mediastino-pulmonary involvement was the most frequent (72.3%), followed by neurological involvement (58.5%), cutaneous involvement (50.8%) and ophthalmological involvement (40%). Genetic analysis showed a high frequency of the HLA DRB1 * 1501 allele (38%), DD genotype (30%) and D allele (54%) of the ACE gene. Treatment with corticosteroids was most often used 73.85%. The evolution was favorable in 13 cases (26.15%), and stable in 63% of cases. In conclusion, sociodemographic and genetic characteristic are variable from one ethnic to another. Advances in genotyping and statistical analysis are helping to elucidate the genetics of sarcoidosis.

Glycogen storage disease type XII; an ultra rare cause of hemolytic anemia and rhabdomyolysis: one new case report

Objectives Aldolase A deficiency also known as glycogen storage disease (GSD) XII, is an ultra rare autosomal recessively inherited GSD, associated with hemolytic anemia and rhabdomyolysis. Case presentation Here, we first report a patient with dermatological findings, hemodialysis requirement for rhabdomyolysis, and a novel likely pathogenic c.971C>T (p.A324V) mutation in the ALDOA gene. Conclusions Episodes of rhabdomyolysis can be triggered by febrile illnesses and catabolic processes. Diagnosis should be confirmed by the mutation analysis of ALDOA gene. Treatment includes management of hemolytic anemia and administration of antipyretics during febrile episodes to avoid hemolysis and rhabdomyolysis.

A case of inguinal hernia associated with atypical Dirofilaria repens infection in a dog

Background Dirofilaria repens is a filarioid nematode transmitted by mosquitoes. Adult D. repens are typically localized in the subcutaneous tissue of the host, but other, atypical localizations have also been reported. There have been several reports of clinical cases involving an association of parasites and hernias in both animals and humans. However, it is unclear if parasitic infection can act as a triggering factor in the development of hernias. Methods A 12-year-old dog was referred to a private veterinarian clinic in Satu Mare, northwestern Romania due to the presence of a swelling in the lateral side of the penis (inguinal area). The dog underwent hernia repair surgery during which four long nematodes were detected in the peritoneal serosa of the inguinal hernial sac. One female specimen was subjected to genomic DNA extraction to confirm species identification, based on amplification and sequencing of a 670-bp fragment of the cytochrome c oxidase subunit 1 (cox1) gene. Treatment with a single dose of imidacloprid 10% + moxidectin 2.5% (Advocate, Bayer AG) was administered. Results The nematodes were morphologically identified as adult D. repens, and the BLAST analyses revealed a 100% nucleotide similarity to a D. repens sequence isolated from a human case in Czech Republic. Conclusions We report a case of an atypical localization of D. repens in the peritoneal cavity of a naturally infected pet dog with inguinal hernia and discuss the associations between hernia and parasitic infections.