Over 150 different proteins attach to the plasma membrane using glycosylphosphatidylinositol (GPI) anchors. Mutations in 18 genes that encode components of GPI-anchor biogenesis result in a phenotypic spectrum that includes learning disability, epilepsy, microcephaly, congenital malformations and mild dysmorphic features. To determine the incidence of GPI-anchor defects, we analysed the exome data from 4293 parent–child trios recruited to the Deciphering Developmental Disorders (DDD) study. All probands recruited had a neurodevelopmental disorder. We searched for variants in 31 genes linked to GPI-anchor biogenesis and detected rare biallelic variants in PGAP3, PIGN, PIGT (n=2), PIGO and PIGL, providing a likely diagnosis for six families. In five families, the variants were in a compound heterozygous configuration while in a consanguineous Afghani kindred, a homozygous c.709G>C; p.(E237Q) variant in PIGT was identified within 10–12 Mb of autozygosity. Validation and segregation analysis was performed using Sanger sequencing. Across the six families, five siblings were available for testing and in all cases variants co-segregated consistent with them being causative. In four families, abnormal alkaline phosphatase results were observed in the direction expected. FACS analysis of knockout HEK293 cells that had been transfected with wild-type or mutant cDNA constructs demonstrated that the variants in PIGN, PIGT and PIGO all led to reduced activity. Splicing assays, performed using leucocyte RNA, showed that a c.336-2A>G variant in PIGL resulted in exon skipping and p.D113fs*2. Our results strengthen recently reported disease associations, suggest that defective GPI-anchor biogenesis may explain ~0.15% of individuals with developmental disorders and highlight the benefits of data sharing.

Liver abscess is rare in neonates. The present report concerns a preterm neonate with history of antenatal laser ablation therapy (to prevent twin to twin transfusion syndrome), who developed liver abscesses within a few days of life. Conservative treatment with antibiotics led to the normalisation of inflammatory markers, leaving an echogenic (calcified) area in the liver.

Purpose of Review In order to inform patients of their genetic risks, access to the medical records and/or stored samples of their relatives is often helpful. We consider some of the obstacles to such access when these relatives are deceased and suggest how they might be navigated. Recent Findings We explore an issue first highlighted in 2004 by Lucassen et al. (Br Med J 328:952–953, 2004) and re-evaluate it in the wake of novel technologies and mainstreaming of genomic medicine. We find that it is still an issue in practice despite professional guidelines advocating access to familial information (Joint Committee on Genomics in Medicine 2019) and that the Human Tissue Act 2004 is often wrongly constructed as a reason to block access. Access is often obstructed by failing to adopt the necessary relational concept of autonomy that applies in genetic medicine as reported by Horton and Lucassen (Curr Genet Med Rep 7:85–91, 2019) and by considering confidentiality to be absolute, even after death. In response to a recent legal case about the confidentiality of genetic test results, and their disclosure to family members (ABC v St George’s Healthcare NHS Trust 2020), Dove et al. (J Med Ethics 45:504–507, 2019) suggested that a duty to consider the interests of genetic relatives could co-exist alongside a duty of confidentiality to a patient. In this way, healthcare professionals can use professional judgement about the relative value of genetic information to family members. This is equally relevant in accessing deceased relatives’ information. A recent systematic review found a high level of acceptability of postmortem use of genetic data for medical research amongst participants and their relatives, and it is reasonable to assume that this acceptability would extend to clinical practice as reported by Bak et al. (Eur J Hum Genet 28:403–416, 2020). Summary Within clinical practice, access to medical records/samples of deceased relatives is often obstructed unnecessarily, potentially resulting in harm to the living relatives seeking advice. Consent to such access is important but need not be the bureaucratic hurdle that is often imposed.

BackgroundMicrodeletions of 2q23.1 disrupting MBD5 and loss of function mutations of MBD5 cause MBD5‐Associated Neurodevelopmental disorders (MAND). Nearly all reported patients have been isolated cases of de novo origin.MethodsThis study investigates three families with inherited MBD5 mutations from three different Regional Genetics Centres in the UK.ResultsTwo of the parents in the study had MBD5 deletions in a mosaic form. The parent with an MBD5 deletion in an apparently nonmosaic form has a psychiatric disorder in the absence of developmental delay or dysmorphism.ConclusionsInherited forms of MBD5 deletions are rare, but do occur, especially in a mosaic form. The phenotypic spectrum of MAND may be wider than previously thought.

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