The analysis of three markers flanking GJB2 gene suggests a single origin of the most common 35delG mutation in the Moroccan population.

In Caucasian populations a single mutation, 35delG, accounts for the majority of GJB2 gene mediated hearing loss, with carrier frequencies estimated between 2-4%, possibly resulting from a founder effect rather than from a mutational hot spot. In Moroccan population, the 35delG mutation accounts for 90.8% of all GJB2 mutated alleles in deaf patients with a carrier frequency of 2.65%. The aim of this study was to evaluate whether the 35delG mutation has derived from a single origin in the Moroccan population. We enrolled 30 unrelated deaf patients homozygous for the 35delG mutation and 165 unrelated control individuals negative for this mutation, and genotyped three microsatellite markers flanking the GJB2 region: D13S141, D13S175 and D13S143. Data analysis revealed that the 35delG mutation is associated with particular alleles of these markers, with significant linkage disequilibrium for the 125 and 105 nucleotide long alleles of D13S141 and D13S175, and that a single specific haplotype accounts for 68% of the chromosomes carrying the 35delG mutation. The estimate age of 35delG mutation is 135 generations or approximately 2700 years old. Like in other Mediterranean populations, our results suggest that in the Moroccan population the 35delG mutation has derived from a single origin in a common founder process.

No association between T222P/LGR8 mutation and cryptorchidism in the Moroccan population.

BACKGROUND: Cryptorchidism is the most common genital anomaly in men. The INSL3/LGR8 system is involved in testicular descent via gubernacular development. INSL3 binds with high affinity to its receptor LGR8 and receptor activation is associated with cAMP signaling. Analysis of human INSL3 and LGR8 mutations confirms that some cases of cryptorchidism are caused by mutations in these genes. The T222P mutation is the only one within the LGR8 gene associated with the cryptorchidism phenotype. A strong association of the T222P mutation with cryptorchidism was found in an Italian population. Due to the same mutation being found in patients within the Mediterranean area, a possible founder effect of this mutation is supposed. METHODS: We screened 109 patients with cryptorchidism and 250 controls in a Moroccan population. RESULTS: We found that 3 of the 109 patients tested carry the T222P mutation and 4 individuals in the control group also carry the mutation. CONCLUSIONS: Our results show in fact that the same mutation is present in the Moroccan population, but an association between cryptorchidism and the T222P mutation was not found.

Absence of GJB3 and GJB6 mutations in Moroccan familial and sporadic patients with autosomal recessive non-syndromic deafness.

UNLABELLED: Deafness is an etiologically heterogeneous trait with a wide variety of genetic and environmental causes. It is generally considered that genetic factors account for at least half of all cases of profound congenital deafness, which can be classified in two categories - dominant or recessive - according to the mode of inheritance and in two types - syndromic or non-syndromic - according to the presence or absence of some other specific clinical features. Mutations in the gene GJB2, encoding the gap junction protein connexion 26, are considered to be responsible for up to 50% of familial cases of autosomal recessive non-syndromic hearing loss and for up to 15-30% of the sporadic cases. It has also been reported that mutations in the GJB6 and GJB3 genes contribute to autosomal recessive and autosomal dominant hearing defects in many populations. OBJECTIVE: The aim of this study was to screen mutations in GJB6 and GJB3 genes in Moroccan patients with autosomal non-syndromic hearing loss. METHODS: We carried out 95 patients with non-syndromic hearing loss. The patients, who were negative for homozygous mutations in GJB2 gene and GJB6-D13S1830 deletion, were tested for the coding regions of GJB6 and GJB3 genes by direct sequencing. RESULTS: No deleterious mutation in GJB6 and GJB3 genes was detected in all deaf patients tested. Only a C357T silent transition in heterozygous state was found in the GJB3 gene in one patient. CONCLUSION: The present data demonstrated that mutations in the GJB6 and GJB3 genes are an infrequent cause of non-syndromic deafness in Morocco.

AZF microdeletions and partial deletions of AZFc region on the Y chromosome in Moroccan men.

AIM: To evaluate for the first time the frequency of Y chromosome microdeletions and the occurrence of the partial deletions of AZFc region in Moroccan men, and to discuss the clinical significance of AZF deletions. METHODS: We screened Y chromosome microdeletions and partial deletions of the AZFc region of a consecutive group of infertile men (n = 149) and controls (100 fertile men, 76 normospermic men). AZFa, AZFb, AZFc and partial deletions of the AZFc region were analyzed by polymerase chain reaction (PCR) according to established protocols. RESULTS: Among the 127 infertile men screened for microdeletion, four subjects were found to have microdeletions: two AZFc deletions and two AZFb+AZFc deletions. All the deletions were found only in azoospermic subjects (4/48, 8.33%). The overall AZFc deletion frequency was low (4/127, 3.15%). AZF microdeletions were not observed in either oligoasthenoteratozoospermia (OATS) or the control. Partial deletions of AZFc (gr/gr) were observed in a total of 7 of the 149 infertile men (4.70%) and 7 partial AZFc deletions (gr/gr) were found in the control group (7/176, 3.98%). In addition, two b2/b3 deletions were identified in two azoospermic subjects (2/149, 1.34%) but not in the control group. CONCLUSION: Our results suggest that the frequency of Y chromosome AZF microdeletions is elevated in individuals with severe spermatogenic failure and that gr/gr deletions are not associated with spermatogenic failure.

Novel mutations involving the INSL3 gene associated with cryptorchidism.

PURPOSE: Cryptorchidism affects 1% to 9% of full-term male neonates. Hypospadias is the second most frequent congenital anomaly seen in newborn males. These pathological conditions are part of the testicular dysgenesis syndrome. Insulin-like factor 3 and LGR8 (leucine-rich repeat-containing G protein-coupled receptor 8), acting as a hormone and a receptor, respectively, are involved in control of the first phase of testicular descent via gubernacular development. MATERIALS AND METHODS: The study group consisted of 184 patients, of whom 52 presented with unilateral cryptorchidism, 37 presented with bilateral cryptorchidism, 19 presented with cryptorchidism and hypospadias, 1 presented with bilateral cryptorchidism and micropenis, and 75 presented with isolated hypospadias. A control panel consisted of 270 controls, including 127 fertile, and 143 fertile noncryptorchid males. Insulin-like factor 3 mutations were analyzed by direct sequencing and restriction enzyme digestion. We analyzed the ability of the mutant insulin-like factor 3 peptides identified in this study to activate LGR8 receptor in an ex vivo assays. RESULTS: We identified 3 novel insulin-like factor 3 variants, including C-19G, V18M and R105H, in 3 of the 109 patients (2.75%) but in none of the 270 controls. The V18M mutation in the insulin-like factor 3 signal peptide had a significant deleterious effect in activating LGR8 receptor in ex vivo studies (p<0.05). To our knowledge we report the first variant in the promoter region of the insulin-like factor 3 gene in a patient with cryptorchidism in association with micropenis. CONCLUSIONS: Mutations involving the insulin-like factor 3 gene may contribute to other anomalies of male genital development, such as micropenis.