A Novel Homozygous Mutation in the COL4A4 Gene (Gly1436del) Causing Alport Syndrome Exposed by Pregnancy: A Case Report and Review of the Literature

Background. Alport syndrome results from a hereditary defect of collagen IV synthesis. This causes progressive glomerular disease, ocular abnormalities, and inner ear impairment. Case Presentation. Herein, we present a case of Alport syndrome in a 28-year-old woman caused by a novel mutation (Gly1436del) in the COL4A4 gene that was not unveiled until her first pregnancy. Within the 29th pregnancy week, our patient presented with massive proteinuria and nephrotic syndrome. Light microscopic examination of a kidney biopsy showed typical histological features of segmental sclerosis, and electron microscopy revealed extensive podocyte alterations as well as thickness of glomerular basement membranes with splitting of the lamina densa. One and a half years after childbirth, renal function deteriorated to a preterminal stage, whereas nephrotic syndrome subsided quickly after delivery. Conclusion. This case report highlights the awareness of atypical AS courses and emphasizes the importance of genetic testing in such cases.

HEREDITARY LOAD IN MEAT AND EGG CHICKENS OF VARIOUS ORIGIN

The aim of the study was to determine the spectrum and frequency of hereditary genetic defects of embryo development in meat and egg hens of different genetic origin, obtained during an experiment to study the effectiveness of crossing roosters of imported meat crosses with meat and egg females of domestic selection. All embryos that died during egg incubation were carefully examined to detect morphopathology. The main research method is pathomorphological analysis of genetic defects of dead embryos. The spectrum and frequency of morphological and anatomical hereditary defects of embryos were established during pathological and anatomical examination of incubation waste. During the autopsy of dead embryos, morphological disorders in the structure of the skeleton were determined, as well as various disproportions of its individual parts. In the meat-egg hens of the original maternal form during three years of monitoring with the highest frequency (2.11–6.06%) revealed such a defect in embryo development as "donald duck". This indicates that the bird is "contaminated" with a "harmful gene" that causes this abnormality. It is worth noting that in groups of chickens that were artificially inseminated with the semen of roosters of meat crosses, this hereditary defect was also recorded. In the descendants of the first and second generations, this anomaly was absent, possibly due to its transition to a heterozygous state. Thus, we can conclude that the allele that expresses this lethal has in its genotype a bird of the local subpopulation "K". Only in meat and egg hens of domestic selection a wide variety of double anomalies was found – four species with a frequency of 1.05–1.12%. Most likely, double abnormalities are the result of homozygosity of dead embryos simultaneously for two lethal genes. Whereas, in chickens of other studied groups, only single anomalies of dead embryos were found, among them "exencephaly", "crossed beak", "shortened beak". Genetic defect of embryos "exencephaly" was found in chickens of most groups. It is obvious that the gene that determines the manifestation of this anomaly is significantly distributed in meat and egg hens of domestic selection and roosters used crosses. And in chickens of the created synthetic population "K-5" only this hereditary defect is revealed. In meat and egg hens of subpopulation "K" (F10) of the original maternal form and in the group of females, which were inseminated with polysperm of meat cocks of the cross "Cobb-500", with a low frequency (0.78–1.12%) a single "crossed beak" anomaly was found among the frozen embryos. This anomaly was not detected in the offspring of the first generation and in groups of chickens inseminated with semen of overripe brood stock. And only in the "cobb" bird of the "K-51" group among the hereditary defects of the dead embryos was this anomaly identified. In meat-egg hens of F10 subpopulation "K" with a low frequency (1.12%) was found a hereditary defect of embryos "shortened beak". Then this anomaly was found only in the "cobb" bird of both the first and second generation. The data show that the hereditary factor that determines this defect, the descendants inherited from the cocks of the cross "Cobb-500". The level of genetic burden in meat and egg hens of the local subpopulation "K", depending on the generation, ranged from 5.26 to 8.99% and was wavy in nature. In the descendants of the first generation it is low – 1.64–4.17%, in the "ross" crossbreeds is much smaller compared to the "cobb". The descendants of the second generation of different origins also had a low hereditary burden – in the range of 4.35–5.88%, which does not exceed the maximum allowable species value of 8.0%. The results of the research showed that crossing meat-egg hens of domestic selection with roosters of imported meat crosses "Cobb-500" and "Ross-308" did not lead to significant "contamination" of genotypes of F1-F2 offspring with lethal genes. This indicates a low share in the heredity of the used offspring of hidden carriers of "defective" genes. This may be due to the high selection of birds of foreign crosses, which does not contribute to the accumulation in its gene pool of lethal genes that cause embryonic developmental abnormalities. In chickens of the created synthetic population "K-5" the level of genetic burden is low (3.03%), which indicates the relative "purity" of this bird from lethal genes.

GOD’S SELF-COMMUNICATION IN HISTORY

God’s communication in history finds fulfilment in Jesus Christ. The refusal of God’s self-communication diminishes the right use of freedom and in the final analysis, the person becomes what he should not become. This is what actually happened to Adam and Eve after eating the forbidden fruit – and we have all inherited that defect – that potency to sin. This situation can be compared to that of hereditary defect in which a defect is passed on from one person to the other. In this case, we can analogously say that all the descendants of Adam have inherited the possibility that we could abuse freedom – by choosing wrong things and this abuse of freedom was redeemed by Jesus Christ.

OBSERVATION ON CONGENITAL LOCO, A HEREDITARY DEFECT IN THREE FLOCKS OF CHICKEN AT IBADAN

Congenital loco, a monogenic, sex-linked hereditary defect was observed in three flocks of chicken at Ibadan. Mortality at the end of the first 4 days of life was unexplainably bigh. Noticeable signs were birds thrown off balance with necks thrown backward s, chicks unable to feed nor drink. Subsequently, they got weak, slumped and died.

Hereditary defect of cobalamin metabolism with adolescence onset resembling multiple sclerosis: 41-year follow up in two cases

The cblC defect is the most common inborn error of cobalamin (Cbl) metabolism. Clinical severity and presentation of the cblC defect ranges from death to mild disability. Only 71 cases of late-onset cblC defect have been described in the literature. We provide the 41-year follow up of two siblings with a late-onset cblC defect, first described after initial diagnosis in 1996. While one of the siblings showed initial symptoms resembling multiple sclerosis with a good response to corticosteroids, the other sister showed only subclinical signs of the disease. The course of the first case was characterized by a severe deterioration and intensive-care therapy after respiratory failure. After diagnoses and Cbl treatment, the patient survived and showed a pronounced improvement of the symptoms. Both sisters have an active life and gave birth to healthy children. The reason for the initial improvement after corticosteroids could not be explained by the classical metabolic pathways of Cbl. Recent studies have suggested that Cbl plays an important role as a regulator of the balance between neurotrophic and neurotoxic factors in the central and peripheral nervous system (CNS and PNS). This first long-term follow up revealed that ultra-high-dose intramuscular Hydroxocobalamin (OH-Cbl) treatment can effectively protect patients from disease progression. It underlines the importance of diagnostic vigilance and laboratory work up even in cases without typical hematologic signs of Cbl deficiency. Cbl-related diseases are often a chameleon and must always be considered in the differential of demyelinating diseases of the PNS and CNS. The case supports the theory that it is not only the classical biochemical pathways that play a key role in Cbl deficiency, especially with regard to neurological symptoms.