Genotype of subjects with borderline hemoglobin A2 levels: Implication for, β-thalassemia carrier screening

In this study, we have defined by molecular analysis, the α, β, and δ globin genotype in a group of individuals with normal or thal-like red cell indices but borderline hemoglobin (Hb)A2 levels, who were identified in a program for β-thal carrier screening. In 37 of 125 individuals with borderline HbA2 levels, we detected a molecular defect in the β, in both the δ and the β, or in the α globin gene. Specifically seven of these subjects were carriers of the ?101 C T mutation, ten of the IVSI nt6 T C mutation, 16 were double heterozygotes for δ and β thal, and two had the triple α globin gene and two the single α globin gene deletion. From these results, we may conclude that subjects with borderline HbA2, particularly when they marry a typical β-thal carrier, should be extensively investigated in order not to miss heterozygous β-thalassemia. © 1994 Wiley-Liss, Inc.     

Hematopoietic stem cell transplantation for curing children with severe autoimmune diseases: Is this a valid option?

The cure of children with severe AD, especially patients with severe, progressive, and therapy-resistant autoimmunity, represents a challenge for current medical practice. The idea of HSCT as a promising therapeutic opportunity was borne accidentally from finding patients who, after undergoing HSCT for a hematological indication, were cured of a concomitant AD. Thus, over the last two decades, HSCT has been extensively investigated, and it has become an appealing therapy for rheumatological (juvenile rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis) and hematological diseases (immune cytopenias). Recently, interesting results have been also described in type 1 diabetes mellitus and Crohn's disease. Although the use of HSCT has been steadily rising in the last few years, many questions are still open, especially after the discoveries of many new biological agents. Given the low incidence of ADs in children, most of the data about the use of the HSCT for these diseases are taken from a mixed cohort of adults and children. The aim of this review is to summarize the published studies and to try to answer the question as to whether this procedure can be considered a promising approach.     

Ask-Upmark kidney and tubulointerstitial nephritis in a woman with severe renal failure

Ask-Upmark kidney is a rare diagnosis of segmental hypoplasia in pediatric population clinically characterized by severe hypertension potentially treatable with partial to total nephrectomy. Although originally was described only as a congenital anomaly, recent data suggest to be caused by vesicoureteral reflux, either in utero or in early childhood and pyelonephritis. The case we reported indicates that Ask-Upmark kidney should be considered as potential cause of hypertension and renal failure both in children and adults. The renal biopsy is necessary for early diagnosis and may consent to normalize blood pressure with nephrectomy; however, if renal damage is severe and progressive with tubulointerstitial nephritis, surgical management is excluded and renal transplant should be considered.     

A 127 kb truncating deletion of PGRMC1 is a novel cause of X-linked isolated paediatric cataract

Inherited paediatric cataract is a rare Mendelian disease that results in visual impairment or blindness due to a clouding of the eye’s crystalline lens. Here we report an Australian family with isolated paediatric cataract, which we had previously mapped to Xq24. Linkage at Xq24–25 (LOD = 2.53) was confirmed, and the region refined with a denser marker map. In addition, two autosomal regions with suggestive evidence of linkage were observed. A segregating 127 kb deletion (chrX:g.118373226_118500408del) in the Xq24–25 linkage region was identified from whole-genome sequencing data. This deletion completely removed a commonly deleted long non-coding RNA gene LOC101928336 and truncated the protein coding progesterone receptor membrane component 1 (PGRMC1) gene following exon 1. A literature search revealed a report of two unrelated males with non-syndromic intellectual disability, as well as congenital cataract, who had contiguous gene deletions that accounted for their intellectual disability but also disrupted the PGRMC1 gene. A morpholino-induced pgrmc1 knockdown in a zebrafish model produced significant cataract formation, supporting a role for PGRMC1 in lens development and cataract formation. We hypothesise that the loss of PGRMC1 causes cataract through disrupted PGRMC1-CYP51A1 protein–protein interactions and altered cholesterol biosynthesis. The cause of paediatric cataract in this family is the truncating deletion of PGRMC1, which we report as a novel cataract gene.Subject terms: Genetic linkage study, Next-generation sequencing     

Pregnancy and human herpesvirus 8 reactivation in human immunodeficiency virus type 1-infected women

To investigate the impact of pregnancy on human herpesvirus 8 (HHV-8) reactivation in human immunodeficiency virus type 1 (HIV-1)-infected women, the HHV-8 DNA presence and load were analyzed in peripheral blood mononuclear cells (PBMCs) and cervicovaginal secretions (CVSs) from 15 pregnant women coinfected with HIV-1 and HHV-8. HHV-8 detection was analyzed in relation to anti-HHV-8 antibodies and HIV-1-related parameters. Nucleotide sequence analysis of an ORFK1 hypervariable region of the HHV-8 strains was performed. HHV-8 was detected in maternal PBMCs (5/15 women) from the second trimester and in CVSs (5/15 women) mainly from the third trimester. The HHV-8 load significantly increased late in pregnancy in both maternal compartments and was associated with a significant increase in HIV-1 shedding in the genital tract. Antilytic antibodies were significantly more common in HHV-8 DNA-positive women. An elevated HHV-8 load was found in the PBMCs of an infant born to a mother with large amounts of HHV-8 in both compartments at delivery. Different ORFK1 subtypes were found in maternal samples, whereas the same subtype was identified in the mother-child pair. These data suggest that pregnancy may induce HHV-8 replication in HIV-1-infected women. An augmented HHV-8 load may, in turn, influence mother-to-child transmission, since one of the HIV-1-infected mothers with HHV-8 reactivation transmitted her ORFK1 subtype to the infant, who showed a high level of HHV-8 viremia indicative of a primary infection. This finding documents for the first time the perinatal transmission of a specific HHV-8 subtype. Vertical transmission may thus play a role in HHV-8 spread also in areas of subendemicity among HIV-1-infected women.     

A comparison between delusional and non-delusional depressives.

Delusional depressive episodes may represent more sever degrees of depressive manifestations or a distinct subtype of depressive illness. To test these two alternative hypotheses, characteristics on demographic, clinical and symptomatic variables, presence of personality disorders and familial loading were compared in 57 delusional and 57 non-delusional depressive patients. The delusional group did not differ on symptomatological intensity degree, clinical and familial loading characteristics. They did differ on higher distribution of Cluster 1 personality disorders. In the delusional sample the presence of mood incongruent psychotic features and hallucinations were evaluated as possible indicators of different subtypes of delusional depression.