Septo-optic dysplasia: clinical study and elements of genetic counseling

The authors report two cases of optic hypoplasia associated with neurological abnormalities and discuss the anatomical, pathophysiological and genetic aspects of the "Septo-Optic Dysplasia". This syndrome is not a homogeneous condition. Available data suggest that the septo-optic dysplasia occurs as a consequence of an embryofoetopathy and not of a genetically determined failure of development. The genetic counselling is described.     

Identification of rare variants causing urea cycle disorders: A clinical,genetic, and biophysical study

Urea cycle disorders (UCDs) are a group of rare metabolic conditions characterized by hyperammonemia and a broad spectrum of phenotypic severity. They are caused by the congenital deficiency in the eight biomolecules involved in urea cycle. In the present study, five cases of UCD were recruited and submitted to a series of clinical, biochemical, and genetic analysis with a combination of high throughput techniques. Moreover, in silico analysis was conducted on the identified missense genetic variants. Various clinical and biochemical indications (including profiles of amino acids and urinary orotic acids) of UCD were manifested by the five probands. Sequence analysis revealed nine diagnostic variants, including three novel ones, which caused Argininosuccinic aciduria (ASA) in one case, Carbamoyl phosphate synthetase 1deficiency (CPS1D) in two cases, Ornithine transcarbamylase deficiency (OTCD) in one case, and Citrin deficiency in 1case. Results of in silico biophysical analysis strongly suggested the pathogenicity of each the five missense variants and provided insight into their intramolecular impacts. In conclusion, this study expanded the genetic variation spectrum of UCD, gave solid evidence for counselling to the affected families, and should facilitate the functional study on the proteins in urea cycle.     

Prader-Willi syndrome: genetic tests and clinical findings

Here we describe the genetic studies performed in 53 patients with the suspected diagnosis of Prader-Willi syndrome (PWS). PWS is characterized by neonatal hypotonia, hypogonadism, delayed psychomotor development, hyperphagia, obesity, short stature, small hands and feet, learning disabilities, and obsessive-compulsive behavior. Through the methylation analysis of the SNRPN gene, microsatellite studies of loci mapped within and outside the PWS/AS region, and fluorescence in situ hybridization (FISH) study, we confirmed the diagnosis in 35 patients: 27 with a paternal deletion, and 8 with maternal uniparental disomy (UPD). The clinical comparisons between deleted and UPD patients indicated that there were no major phenotype differences, except for a lower birth length observed in the UPD children. Our sample was composed of more girls than boys; UPD patients were diagnosed earlier than the deleted cohort (2(10/12) s. 7(9/12) years); and, in the deleted group, the boys were diagnosed earlier than the girls (5(2/12) vs. 7(8/12) years, respectively).     

Hereditary deafness in Kirov oblast: A genetic epidemiological study

The results of a genetic epidemiological study of hereditary deafness (HD) in ten raions (districts) of Kirov oblast (administrative region), Russia, are presented. A total of 122 075 people have been examined. Segregation analysis of all families with diagnosed HD has demonstrated a good fit to either the autosomal dominant (AD) or autosomal recessive (AR) mode of inheritance. The total prevalence rates of AD and AR HDs, as well as the specific prevalence rates of nonsyndromic and syndromic forms of HD, have been calculated for the population of ten raions. The HD prevalence rate in Kirov oblast has been found to be 1: 1043 people (1: 1453 and 1: 3699 for the nonsyndromic and syndromic forms, respectively). This value has been found to vary in different raions, which is explained by differences in the genetic subdivision levels of the populations studied; the correlation coefficient between the HD load and random inbreeding (F _ST) in district populations is r = 0.81 ± 0.22. The diversity of syndromic hearing disorders is described.