Prevalence of specific and recurrent/founder pathogenic variants in BRCA genes in breast and ovarian cancer in North Africa.

BACKGROUND: Elucidation of specific and recurrent/founder pathogenic variants (PVs) in BRCA (BRCA1 and BRCA2) genes can make the genetic testing, for breast cancer (BC) and/or ovarian cancer (OC), affordable for developing nations. METHODS: To establish the knowledge about BRCA PVs and to determine the prevalence of the specific and recurrent/founder variants in BRCA genes in BC and/or OC women in North Africa, a systematic review was conducted in Morocco, Algeria, and Tunisia. RESULTS: Search of the databases yielded 25 relevant references, including eleven studies in Morocco, five in Algeria, and nine in Tunisia. Overall, 15 studies investigated both BRCA1 and BRCA2 genes, four studies examined the entire coding region of the BRCA1 gene, and six studies in which the analysis was limited to a few BRCA1 and/or BRCA2 exons. Overall, 76 PVs (44 in BRCA1 and32 in BRCA2) were identified in 196 BC and/or OC patients (129 BRCA1 and 67 BRCA2 carriers). Eighteen of the 76 (23.7%) PVs [10/44 (22.7%) in BRCA1 and 8/32 (25%) in BRCA2] were reported for the first time and considered to be novel PVs. Among those identified as unlikely to be of North African origin, the BRCA1 c.68_69del and BRCA1 c.5266dupC Jewish founder alleles and PVs that have been reported as recurrent/founder variants in European populations (ex: BRCA1 c.181T>G, BRCA1 c1016dupA). The most well characterized PVs are four in BRCA1 gene [c.211dupA (14.7%), c.798_799detTT (14%), c.5266dup (8.5%), c.5309G>T (7.8%), c.3279delC (4.7%)] and one in BRCA2 [c.1310_1313detAAGA (38.9%)]. The c.211dupA and c.5309G>T PVs were identified as specific founder variants in Tunisia and Morocco, accounting for 35.2% (19/54) and 20.4% (10/49) of total established BRCA1 PVs, respectively. c.798_799delTT variant was identified in 14% (18/129) of all BRCA1 North African carriers, suggesting a founder allele. A broad spectrum of recurrent variants including BRCA1 3279delC, BRCA1 c.5266dup and BRCA2 c.1310_1313detAAGA was detected in 42 patients. BRCA1 founder variants explain around 36.4% (47/129) of BC and outnumber BRCA2 founder variants by a ratio of ≈3:1. CONCLUSIONS: Testing BC and/or OC patients for the panel of specific and recurrent/founder PVs might be the most cost-effective molecular diagnosis strategy.

Evaluation of ultrasensitive CRP and microalbuminuria as cardiovascular risk markers in type 2 diabetic moroccan patients.

INTRODUCTION: Type 2 diabetes is a chronic disease whose prevalence is increasing exponentially. This condition is a risk factor for cardiovascular disease, the leading cause of death among diabetics. AIM: To study the correlation between hs CRP, microalbuminuria, diabetes monitoring parameters and the presence of vascular complications in a group of non-insulin dependent diabetic patients followed in endocrinology department of the Moulay Ismail Military Hospital in Meknes. METHODS: The study involved 250 patients with type 2 diabetes and 120 control subjects. Patients were subduvised on 2 groups: group I consisting of patients without diabetes vascular complications. Group II involved patients with at least one vascular complication. The parameters measured were age, sex, BMI, duration of diabetes and the presence of vascular complications. The studied biological parameters were hs CRP, microalbuminuria, HbA1c and lipid profile. RESULTS: Diabetic patients with complications had significantly higher levels of hs CRP and microalbuminuria compared with diabetic patients without complications and with controls (8.37 vs 5.94 vs 2.63; p <0.001 vs 62.10 34 56 vs 5.67; p <0.0001). The rate of hs CRP were significantly correlated with HA1c, total cholesterol, the LDL-C, index atherogenicity microalbuminuria and duration of diabetes for the two patient groups. A significant correlation between hs CRP and age was only found in Group I. CONCLUSION: CRP appears to be interested in the detection of vascular complications in diabetic type2.

Clinical Significance of Somatic Mutations in RAS/RAF/MAPK Signaling Pathway in Moroccan and North African Colorectal Cancer Patients.

BACKGROUND: Mutations in RAS (KRAS, NRAS) and BRAF genes are the main biomarker predicting response to anti-EGFR monoclonal antibodies in targeted therapy in colorectal cancer (CRC). OBJECTIVE: Our study aims to evaluate the frequencies of KRAS, NRAS and BRAF mutations and their possible associations with clinico-pathological features in CRC patients from Morocco. METHODS: DNA was extracted from 80 FFPE samples using the QIAamp DNA FFPE-kit. RAS and BRAF mutations were assessed by pyrosequencing assays using Qiagen, KRAS Pyro®kit 24.V1, Ras-Extension Pyro®kit 24.V1 and BRAF Pyro®Kit 24.V1, respectively, and carried out in the PyroMark-Q24. RESULTS: RAS mutations were identified in 57.5% (56.2% in KRAS, 8.8% in NRAS). In KRAS gene, exon 2 mutations accounted for 93.3% (68.9% in codon 12, 24.4% in codon 13). Within codon 12, G12D was the most prevalent mutation (37.7%), followed by G12C (13.4%), G12S (8.9%) and G12V (6.6%). Within codon 13, the most frequently observed mutation was G13D (22.3%). The mutation rates of exon 3 and 4 were 15.6% and 13.3%, respectively. In exon 3 codon 61, 2.3% patients were detected with two concurrent mutations (Q61R, Q61H), and 4.4% with three concurrent mutations (Q61R, Q61H, Q61L). In NRAS gene, the mutation rates of exon 2, 3 and 4 were 57.1%, 28.6%, and 14.3%, respectively. G13A and Q61H were the most common mutations, accounting for 42.9% and 28.5%, respectively. There were 13% patients with concurrent KRAS/NRAS mutation and 4.3% wt KRAS with NRAS mutations. No mutations were identified in BRAF gene. In both sexes, KRAS codon 12 mutations were associated with higher stage III/IV tumors. Moreover, Patients whose tumor is in the proximal colon (56.3%) are more likely to harbor KRAS mutations than those tumor located in rectum (25%). CONCLUSION: RAS mutations could be useful in future target anti-EGFR therapy and molecular CRC screening strategy in Morocco.

[Bilateral pleurisy revealing a myelome with free light chains complicated with an osseous amylose]. / Pleurésie bilatérale révélant un myélome à chaînes légères compliqué d'une amylose osseuse.

The osseous amyloidosis associated with a pleural effusion in a myeloma is a rare situation. We report a case of an association of these three disease entities for discussion. A 75-year-old man was admitted for chest pain and dyspnea with left sacred bone pain. The radiological assessment reported pleurisy and bilateral lytic images of the sacrum with soft tissue invasion, the biochemical tests showed a lambda free light chain myeloma and bone biopsy reported amyloidosis. The occurrence of systemic amyloidosis in myeloma is well documented, but the osseous location is rare and rarely revealed. Pleural effusion is a known complication of myeloma but is exceptionally revealing; it is usually seen in the myeloma IgG and IgA but very rarely in free light chain myeloma. We reported here a case that represents an exceptional situation of complications of light chains myeloma to remember their possible occurrence and to insist for the clinician sensitizing to carry out investigations on time and avoid complications or at minimum to retard them.

[Fahr syndrome secondary to primary hypoparathyroidism: about a case]. / Syndrome de Fahr secondaire à une hypoparathyroïdie primaire: à propos d'un cas.

Fahr syndrome is a rare anatomo-clinic disease whose most common cause is primary or postoperative hypoparathyroidism. It is characterized by bilateral and symmetrical intracerebral calcifications located in the central gray nuclei, most often associated with phosphocalcium metabolism disorders. We here report the case of a 54-year old patient who had been treated for primary hypoparathyroidism for 20 years, presenting with amnesic disorders revealing Fahr syndrome secondary to hypoparathyroidism.

[Idiopathic capillary hyperpermeability syndrome revealing of Waldenström disease]. / Un syndrome d'hyperperméabilité capillaire idiopathique révélant une maladie de Waldenström.

Waldenstrom disease is a rare hematologic disorder characterized by lymphoplasmacytic proliferation associated with the production of monoclonal IgM. Visceral injuries are described but some are rare (lung), others never reported (cardiac). We report for information and discussion a case representing these particular situations, considering that these attacks were revealing. It is a 63 year old man who was admitted to the emergency room in an array of tamponade, with edema at the front and four members. Clinical and radiological examinations were objectified bilateral pleural effusion, ascite and pericarditis. The biological exploration showed pancytopenia, serum proteins 120 g/L and a monoclonal peak migrant beta2 globulin electrophoresis which is made by monoclonal immunoglobulin M (IgM kappa). The bone marrow confirmed the diagnosis of the Waldenström disease. This is a mode of revelation never described before. Considering this case, it would be wise to think of a Waldenström disease before any polyserositis.

[Another case of the rare complications of chronic lymphocytic leukemia: angioedema]. / Encore un cas de complication rare des leucémies lymphoïdes chroniques : l'œdème angioneurotique.

Angioedema is a rare but may be serious (laryngeal edema). This is a recurrent edema, subcutaneous and/or submucosal, whose cause is a hereditary or acquired deficiency in C1 inhibiteur (C1 inhibitor fraction of complement). We present the case of a 56 years old patient who showed recurrent episodes of swelling of the face and hands in association with chronic lymphocytic leukemia stage A. The exploration of the complement pathway has allowed retaining the diagnosis of acquired angioedema type I. The association of angioedema and lymphoproliferative syndrome is rare; we present this interesting case to discuss it from the literature data.