Subject(s)
Connexin 43/genetics , Craniofacial Abnormalities/genetics , DNA Mutational Analysis , Eye Abnormalities/genetics , Foot Deformities, Congenital/genetics , Syndactyly/genetics , Tooth Abnormalities/genetics , Adult , Chromosome Aberrations , Craniofacial Abnormalities/diagnosis , Exons/genetics , Eye Abnormalities/diagnosis , Female , Foot Deformities, Congenital/diagnosis , Genes, Dominant , Humans , Infant , Infant, Newborn , Male , Middle Aged , Pedigree , Phenotype , Syndactyly/diagnosis , Tooth Abnormalities/diagnosis , TunisiaSubject(s)
46, XX Disorders of Sex Development/genetics , Chromosomes, Human, Pair 8/genetics , Chromosomes, Human, X/genetics , Craniofacial Abnormalities/genetics , Developmental Disabilities/genetics , Mosaicism , Sex Chromosome Aberrations , Trisomy/genetics , Uniparental Disomy/genetics , 46, XX Disorders of Sex Development/diagnosis , Child , Child, Preschool , Craniofacial Abnormalities/diagnosis , Developmental Disabilities/diagnosis , Humans , Muscle Hypotonia/diagnosis , Muscle Hypotonia/genetics , Phenotype , Seizures, Febrile/diagnosis , Seizures, Febrile/genetics , Trisomy/diagnosis , Uniparental Disomy/diagnosisABSTRACT
Steroid 11ß-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, resulting in virilization, glucocorticoid deficiency and hypertension. The 11ß-hydroxylase enzyme is encoded by the CYP11B1 gene and mutations in this gene are responsible for this disease. The aim of this study was to characterize mutations in the CYP11B1 gene and to determine their frequencies in a cohort of Tunisian patients. The molecular genetic analysis was performed by direct nucleotide sequencing of the CYP11B1 gene in 15 unrelated Tunisian patients suffering from classical 11ß-hydroxylase deficiency. Only two mutations were detected in homozygous state in the CYP11B1 gene of all patients, the p.Q356X in exon 6 (26.6%) and the novel p.G379V in exon 7 with large prevalence (73.3%). This is the first report of screening for mutations of CYP11B1 gene in the Tunisian population and even in the Arab population.
Subject(s)
DNA Mutational Analysis , Mutation , Steroid 11-beta-Hydroxylase/genetics , Adrenal Hyperplasia, Congenital/diagnosis , Adrenal Hyperplasia, Congenital/enzymology , Adrenal Hyperplasia, Congenital/genetics , Base Sequence , Codon, Nonsense , Consanguinity , Female , Humans , Male , Mutation, Missense , Polymerase Chain Reaction , Sequence Analysis, DNA , TunisiaABSTRACT
Turner's syndrome (TS) affects about 1/2500 female infants born alive. The syndrome results from total or partial absence of one of the two X chromosomes normally present in females. We report the results of a retrospective analysis of 89 cases of TS observed during a six-year period (2000-2005). The patients' age ranged from two days to 51 years at the time of this analysis. Most patients were adults (48%). The aim of this study is to ascertain the principal clinical features leading to a request for a karyotype, searching for a possible relationship between chromosomal anomalies and clinical expression of TS. Pediatric patients were referred for statural retardation or dysmorphic features, while reproduction anomalies were the main indication for karyotyping in patients aged over 20 years. Mosaicism was prevalent (47%), whereas the homogeneous karyotype 45,X was found in only 32% of the patients; structural anomalies were found in 21%. Regarding the advanced age of our patients, we established a relationship between chromosome anomalies and the clinical expression of TS, based on an analysis of stature and reproduction disorders. Short stature and primary amenorrhea were correlated with total deletion of one chromosome X or imbalanced gene dosage due to structural X anomalies. Whereas cases of infertility, recurrent miscarriages and secondary amenorrhea were associated with a mosaic karyotype pattern (45,X/46,XX or 45,X/46,XX/47,XXX ...), with a slight mosaicism in most cases. Thus, chromosome investigations should be performed in cases of reproduction failure even for women with normal stature.
Subject(s)
Turner Syndrome/genetics , Abortion, Habitual/etiology , Adolescent , Adult , Amenorrhea/genetics , Amenorrhea/pathology , Body Height/physiology , Child , Child, Preschool , Chromosome Aberrations , Chromosomes, Human, X/genetics , Face/abnormalities , Female , Growth Disorders/etiology , Humans , Infant , Infant, Newborn , Infertility, Female/etiology , Karyotyping , Middle Aged , Mosaicism , Retrospective Studies , Tunisia , Turner Syndrome/diagnosis , Young AdultABSTRACT
AIM: To determine frequency of Y microdeletions in azoospermic and oligospermic Tunisian infertile males. METHODS: A Sample of 146 Tunisian infertile males with a low sperm count (<5 x 10(6) sperms per mililiter) and normal karyotype was screened for Y chromosome microdeletions. 76 men were azoospermic and 70 men were oligospermic. Genomic DNA was isolated from blood and multiplex PCR was carried out with a set of 20 AZFa, AZFb and AZFc STS markers to detect the microdeletions as recommended by the European Academy of Andrology. RESULTS: In 10/146 (6.85%) subjects AZF deletions were observed. Of these ten males with microdeletions, 9/10 subjects were azoospermic (90%), 1/10 was oligospermic (10%). Frequency of microdeletions in azoospermic men was 9/76 (11.84%). None of the patients showed isolated microdeletion in the AZFa region, but one azoospermic man had deletion in the AZFb region. Eight azoospermic patients and one oligospremic man have AZFc microdeletions. AZFc and AZFb were deleted in three azoospermic patients. AZFc, AZFb and AZFa were deleted in three azoospermic patients We estimate the sensitivity of the test comprising six STS in our sample to be 90%. CONCLUSION: The incidence of Yq microdeletions in the study population of infertile Tunisian men falls within the range published in other countries. We suggest to analyze 9STS in the first step to detect efficiently Y microdeletions in our population.
