UBE2A deficiency in two siblings: A novel splicing variant inherited from a maternal germline mosaicism

UBE2A deficiency is a syndromic condition of X-linked intellectual disability (ID) characterized by typical dysmorphic features that include synophrys, prominent supraorbital ridges, almond-shaped, and deep-set eyes, large ears, wide mouth, myxedematous appearance, hirsutism, micropenis, and onychodystrophy. To date, only seven familial UBE2A intragenic mutations and nine larger microdeletions encompassing UBE2A have been reported. Here, we describe two siblings with X-linked ID and typical clinical features of UBE2A deficiency caused by a novel hemizygous variant, identified by massively parallel sequencing of X-exome. The synonymous c.330G>A substitution in UBE2A modifies the last nucleotide of exon 5, causing the exon skipping and resulting in an out-of-frame transcript, likely encoding for a truncated form of the ubiquitin-conjugating enzyme E2 A. As confirmed by deep sequencing, the c.330G>A substitution in UBE2A was undetectable in genomic DNA from maternal blood cells, suggesting that the recurrent UBE2A deficiency observed in males of this family is caused by a maternal germline mosaicism.

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Phenotypic heterogeneity of POMT2 gene variants

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A beginner's guide to gene editing

Abstract

Genome editing enables precise changes to be made in the genome of living cells. The technique was originally developed in the 1980′s but largely limited to use in mice. The discovery that a targeted double stranded break (DSB) at a unique site in the genome, close to the site to be changed, could substantially increase the efficiency of editing raised the possibility of using the technique in a broader range of animal models and potentially human cells. But the challenge was to identify reagents that could create targeted breaks at a unique genomic location with minimal off-target effects. In 2005, the demonstration that programmable zinc finger nucleases (ZFNs) could perform this task, led to a number of proof-of-concept studies, but a limitation was the ease with which effective ZFNs could be produced. In 2009, the development of TAL-effector nucleases (TALENs) increased the specificity of gene editing and the ease of design and production. However, it wasn't until 2013 and the development of the CRISPR Cas9/guideRNA that gene editing became a research tool that any lab could use.

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Factors Associated with Vaccination Status of Children Aged 12–48 Months in India, 2012–2013

Abstract

Objectives India has more unvaccinated children than any other country despite provision of free vaccines through the government's Universal Immunization Program. In this study, we calculated the proportion of children aged 12–48 months who were fully vaccinated, under-vaccinated, or who had not received any vaccines. Childhood, household, and sociocultural factors associated with under-vaccination and non-vaccination were evaluated. Methods Using data from India's 4th District-level Health and Facility Survey, 2012–2013 (DLHS-4) and the 2012–2013 Annual Health Survey (AHS), we calculated the proportion of children who were non-vaccinated, under-vaccinated, or fully vaccinated with 1 dose of Bacillus Calmette–Guérin, 3 doses of oral polio vaccine, 3 doses of diphtheria–pertussis–tetanus, and 1 dose of measles-containing vaccine. The odds of full vaccination compared to non-vaccination and under-vaccination relative to various factors was assessed using a multivariable, multinomial logistic regression which accounted for survey design. Results Of 1,929,580 children aged 12–48 months, 59% were fully vaccinated, 34% were under-vaccinated, and 7% were non-vaccinated. Compared to children born in government institutions, children delivered in non-institutional settings with a skilled birth attendant present had higher odds of non-vaccination (OR 1.66) and those without a skilled attendant present had still greater odds of non-vaccination (OR 2.39) and under-vaccination (OR 1.11). Conclusions for Practice India's vaccination rates among children aged 12–48 months remains unacceptably low. The Indian government should encourage institutional delivery or birthing with a skilled attendant to ensure women receive adequate health education through antenatal care that includes the importance of childhood vaccination.

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Irritable bowel syndrome and Endometriosis: new insights for old diseases

Irritable bowel syndrome and endometriosis are two diseases affecting a significant part of the female population, either together or individually, with remarkable consequences in the quality of life. Several studies suggest an epidemiological association between them. Their association may not be just an epidemiological phenomenon, but the manifestation of a pathophysiological correlation, which probably generates a mutual promotion phenomenon. In particular, both clinical entities share the presence of a chronic low-grade inflammatory state at the basis of the disease persistence.

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Nonalcoholic fatty liver disease as a sentinel marker for the development of diabetes mellitus in non-obese subjects

Non-alcoholic fatty liver disease (NAFLD) is associated with substantial cardiometabolic morbidity.

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A tough life in utero doesn't necessarily make for a stiff future: sex matters for aortic passive mechanics

Abstract

Life in utero is not all smooth sailing for some. Even in individuals endowed with a 'perfect' set of genes other factors can conspire to make life less than ideal, inducing physiological adaptations in the fetus, some of which persist from the womb right through to the tomb.

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