Xlag 4.0
Other disorders were 10 cases of heterotopias, 5 schizencephaly, 3 holoprosencephaly, 2 polymicrogyria, and one each of hemimegalencephaly, and hydranencephaly. There were 48 cases of corpus callosum agenesis, and 16 cases of lissencephaly/pachygyria. Corpus callosum agenesis and lissencephaly/pachygyria formed the major group. The MR imaging was used for the diagnosis of a neuronal migration anomaly. The data were collected at the Child Neurology Services of Sultan Qaboos University Hospital, Oman, from January 1993 to September 2006 from all children with psychomotor delay and epilepsy, who underwent brain imaging (mostly MRI). To record the pattern of different neuronal migrational disorders (NMD) and their associated neurological conditions. In addition, digenic inheritance was observed in two of our patients and was suggested to be a cause of the phenotypic variability observed in DSD. WES identified rare and novel pathogenic variants in NR5A1, WT1, HHAT, CYP19A1, AMH, AMHR2, and FANCA and in the X‐linked genes ARX and KDM6A. Our patients showed a different mutational profile compared with that reported in other populations with a predominance of heritable DSD causes. Sanger sequencing identified pathogenic variants in 33.7% of 46,XY patients, while the detection rate of WES reached 66.7%. The study revealed a high rate of sex chromosomal DSD (33%) with a wide array of cytogenetic abnormalities. Whole exome sequencing (WES) was carried out for 18 selected patients. The patients underwent thorough clinical examination, hormonal and imaging studies, detailed cytogenetic and fluorescence in situ hybridization analysis, and molecular sequencing of genes known to commonly cause DSD including AR, SRD5A2, 17BHSD3, NR5A1, SRY, and WT1. This three‐year study included 225 patients with various DSD forms, referred to the genetic DSD and endocrinology clinic, National Research Centre, Egypt. The aim of this work was to identify genetic variants responsible for disorders of human urogenital development in a cohort of Egyptian patients. The molecular analysis of this mutation should be considered as a routine for the genetic diagnosis of mental retardation in males of nondrafted cause.ĭisorders/differences of sex development (DSD) comprise a group of congenital disorders that affect the genitourinary tract and usually involve the endocrine and reproductive system. Personal and familiar history, phenotype and evolution are described. We report three cases of mental retardation in two different families where the mutation in ARX gene c.428_451 dup24 was found while X-fragile syndrome screening was made. It causes an expansion of a polyalanine tract of ARX protein. The most frequent mutation that has been reported is the c.428_451 dup24, which comprises almost 60% of all described. Recently has been demonstrated that mutations in a new called ARX gene (aristaless-related homeobox) can also cause a similar form of X linked mental retardation, as well as other neurological disorders (autism, Partington or West syndrome). This genetic disorder predominantly affects males and it is mainly caused by the expansion of CGG in FMR1 gene. Mental retardation has an approximated prevalence of 2% in the general population and its most frequent cause is X-fragile syndrome. Additional findings were hypercalciuria, vesicoureteral reflux, patent ductus arteriosus and chronic diarrhea. MRI showed diffuse pachygyria, moderate thickening of the cortex, enlarged ventricles, agenesis of the corpus callosum and septum pellucidum. EEG showed disorganized background activity and seizures starting at the right midtemporal, central and occipital regions. Examination identified microcephaly, axial hypotonia, pyramidal signs and ambiguous genitalia.
Second child born to healthy nonconsanguineous parents, presented with seizures within the first hour of life that remained refractory to phenobarbital, phenytoin and midazolam. Patients present with lissencephaly, agenesis of the corpus callosum, refractory epilepsy of neonatal onset, acquired microcephaly and male genotype with ambiguous genitalia. X-linked lissencephaly with ambiguous genitalia (XLAG) is a recently described genetic disorder caused by mutation in the aristaless-related homeobox (ARX) gene (Xp22.13).