Genetics in the Third Millennium
Volume:5 Issue: 1, 2007

Ambiguous genitalia is an important medical problem, so the physicians who see newborns should note to its urgent diagnosis and early decision for rearing gender. The subject of this article is describing the different types of disorders of sex development (DSD), its new classification and approach to the patients. The prevalence of its different types in 282 patients who was seen during 20 years is also reported. 46,XX DSD was the most prevalent type and 97.6% of it was due to congenital adrenal hyperplasia. 46,XY DSD and sex chromosome DSD were seen in 9.2% and 1.4%, respectively.

Peroxisomes are formed either from pre-existing peroxisomes or some endomembrane compartments through de novo pathway. Distinct steps of peroxisome biogenesis which are peroxisome membrane assembly, import of matrix proteins and peroxisome proliferation are conducted by peroxins. Among peroxins, Pex3p, Pex16p and Pex19p act in membrane biogenesis and Pex11p has a role in peroxisome proliferation. Moreover, import of peroxisomal matrix proteins require Pex5p and Pex7p which recognize PTS1- and PTS2- proteins in cytosol. Receptor docking occurs by Pex13p and Pex14p at the membrane of peroxisomes, then Pex2p, Pex10p, Pex12p cause translocation across the peroxisomal membrane and finally receptor recycling is mediated by Pex1p, Pex6p and Pex26p. Mutations in PEX genes encoding peroxins result in peroxisomal disorders which comprise a group of genetically and clinically diverse inborn errors of metabolism. The broadening opportunities for determining and sequencing of these genes is one frontier that remains to be explored and will benefit from ongoing researches

Peroxisome proliferator-activated receptors (PPARs) belong to nuclear receptor family, which act as lipid sensors to modulate gene expression and control cellular fate. PPARs are implicated in different cellular processes such as cellular differentiation, apoptosis, development, immune responses and energy homeostasis. PPARs compose a family of three nuclear receptors that they are termed PPARα, PPARβδ and PPARγ. These receptors demonstrate differential ligand specificities and cellular expression patterns. These PPAR ligands are used to treat type II diabetes mellitus, hypertriglyceridemia and inflammation. Recently, these receptors have been supposed as new targets for the treatment of CNS inflammatory disorders. Throughout this review, we focus on the molecular structure of PPARs, posttranslational modifications that regulate function of these receptors and then molecular mechanisms through which PPARs regulate transcription with particular emphasis on the latest results on corepressors and coactivators actions. Finally, we introduce each PPAR isotype, cellular functions of them and their ligands.

We are reporting a 25 year old man with minor facial and genital anomalies and bilateral ectrodactyly. His parents are first cousins and are both healthy. Facial manifestations included hypertelorism, short down-slanted palpebral fissures, small low-set ears and high forehead. Genital anomalies were undescended right testicle, micropenis and hypospadias. There were four fingers in both hands with a feature of cleft deformity and bone hypoplasia. His sister died four days after birth with severe limb defects and imperforate anus.

Smith-Magenis syndrome (SMS) is a multisystem, neurodevelopmental genetic disorder associated with mental retardation that predisposes individuals to a distinct pattern of maladaptive behaviors and other neuropsychological impairments. A family with a mental retarded male individual suspected of this syndrome were referred to our center for prenatal diagnosis. After genetic counseling, karyotyping was performed for confirmation of the disease. The results indicated that both parents were normal and the affected child had del(17)(p11.2→p12). The chromosomal anomaly with facial characteristics not particularly evident, mental retardation, behavioral troubles, hyperactivity, autistic traits and dysarticulation led to the diagnosis of the Smith-Magenis syndrome.

Fanconi anemia (FA) is an autosomal recessive disorder associated with bone marrow failure and severe birth defects. Early diagnosis of FA permits the proper management of hematologic disease, completion of elective surgery before thrombocytopenia ensues, appropriate genetic counseling, identification of unaffected siblings or pregnancies who might serve as donors for hematopoietic stem/progenitor cells for an FA patient with bone marrow disease, and targeted cancer surveillance. Cytogenetic analysis is the most classical and available test for FA, which involves detection of chromosomal breakage or aberrations in metaphase spreads. We have experienced cytogenetic chromosomal breakage analysis of FA cases for more than 20 years. According to our computerized data, we have received 501 patients (294, 59% male) who were referred to our center for chromosomal breakage study. Cytogenetic analysis of the cases revealed multiple breakages and rearrangements in 92 cases (18%) compatible with Fanconi anemia and normal karyotype were detected in 385 cases (77%). The remaining 24 cases (5%) were failed in culture due to low number of WBC count. Among FA positive cases 50 (54%) were female and 42 (46%) were male.