Molecular Genetics
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Research outputs from the Molecular Genetics department at the RD&E. The Molecular Genetics Laboratory is in the RILD Building at the RD&E and is co-located with University of Exeter Medical School researchers in genetics, genomics and epigenetics. For more information, please visit their website: http://www.exeterlaboratory.com/molecular-genetics/
Recent Submissions
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HNRNPH1-related syndromic intellectual disability: Seven additional cases suggestive of a distinct syndromic neurodevelopmental syndrome
(Wiley, 2020-07)Pathogenic variants in HNRNPH1 were first reported in 2018. The reported individual, a 13 year old boy with a c.616C>T (p.R206W) variant in the HNRNPH1 gene, was noted to have overlapping symptoms with those observed in ... -
Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data
(Elsevier Science, 2019-11-07)Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the ... -
Correction: A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome
(Nature Publishing Group, 2020-05)An amendment to this paper has been published and can be accessed via a link at the top of the paper. -
Correction: Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance
(Nature Publishing Group, 2020-06)An amendment to this paper has been published and can be accessed via a link at the top of the paper. -
Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance
(Nature Publishing Group, 2020-06)Purpose: Diagnosis of genetic disorders is hampered by large numbers of variants of uncertain significance (VUSs) identified through next-generation sequencing. Many such variants may disrupt normal RNA splicing. We examined ... -
Cancer Variant Interpretation Group UK (CanVIG-UK): an exemplar national subspecialty multidisciplinary network
(Highwire, 2020-03-13)Advances in technology have led to a massive expansion in the capacity for genomic analysis, with a commensurate fall in costs. The clinical indications for genomic testing have evolved markedly; the volume of clinical ... -
Expanding Clinical Presentations Due to Variations in THOC2 mRNA Nuclear Export Factor
(Frontiers Media SA, 2020-02-11)Multiple TREX mRNA export complex subunits (e.g., THOC1, THOC2, THOC5, THOC6, THOC7) have now been implicated in neurodevelopmental disorders (NDDs), neurodegeneration and cancer. We previously implicated missense and ... -
Update of variants identified in the pancreatic β-cell K ATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes
(Wiley, 2020-05)The most common genetic cause of neonatal diabetes and hyperinsulinism is pathogenic variants in ABCC8 and KCNJ11. These genes encode the subunits of the β-cell ATP-sensitive potassium channel, a key component of the ... -
Using referral rates for genetic testing to determine the incidence of a rare disease: The minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389
(Public Library of Science, 2020-02-06)ongenital hyperinsulinism (CHI) is a significant cause of hypoglycaemia in neonates and infants with the potential for permanent neurologic injury. Accurate calculations of the incidence of rare diseases such as CHI are ... -
Homozygous Hypomorphic HNF1A Alleles Are a Novel Cause of Young-Onset Diabetes and Result in Sulfonylurea-Sensitive Diabetes
(American Diabetes Association, 2020-04)Objective: Heterozygous loss-of-function mutations in HNF1A cause maturity-onset diabetes of the young (MODY). Affected individuals can be treated with low-dose sulfonylureas. Individuals with homozygous HNF1A mutations ... -
Opposite Modulation of RAC1 by Mutations in TRIO Is Associated with Distinct, Domain-Specific Neurodevelopmental Disorders
(Elsevier Science, 2020-03-05)The Rho-guanine nucleotide exchange factor (RhoGEF) TRIO acts as a key regulator of neuronal migration, axonal outgrowth, axon guidance, and synaptogenesis by activating the GTPase RAC1 and modulating actin cytoskeleton ... -
Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism
(Elsevier Science, 2020-02-06)Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous ... -
Heterozygous Insulin Receptor ( INSR) Mutation associated with Neonatal Hyperinsulinemic Hypoglycaemia and Familial Diabetes Mellitus: Case Series
(Galenos Yayinevi, 2020-01-28)Mutations in the insulin receptor (INSR) gene are associated with insulin resistance and hyperglycaemia. Various autosomal dominant heterozygous INSR mutations leading to hyperinsulinemic hypoglycaemia (HH) have been ... -
A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome
(Springer Nature, 2020-05)Purpose: To investigate if specific exon 38 or 39 KMT2D missense variants (MVs) cause a condition distinct from Kabuki syndrome type 1 (KS1). Methods: Multiple individuals, with MVs in exons 38 or 39 of KMT2D that encode ... -
De Novo Mutations in EIF2B1 Affecting eIF2 Signaling Cause Neonatal/Early-Onset Diabetes and Transient Hepatic Dysfunction
(American Diabetes Association, 2020-03)Permanent neonatal diabetes mellitus (PNDM) is caused by reduced β-cell number or impaired β-cell function. Understanding of the genetic basis of this disorder highlights fundamental β-cell mechanisms. We performed trio ... -
Genomic variant sharing: a position statement
(Wellcome, 2019-02)Sharing de-identified genetic variant data via custom-built online repositories is essential for the practice of genomic medicine and is demonstrably beneficial to patients. Robust genetic diagnoses that inform medical ... -
Patterns of postmeal insulin secretion in individuals with sulfonylurea- treated KCNJ11 neonatal diabetes show predominance of non- KATP- channel pathways
(BMJ, 2019-12)Insulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-KATP-channel pathways such as incretins. Affected individuals ... -
Prediction algorithms: pitfalls in interpreting genetic variants of autosomal dominant monogenic diabetes
(American Society for Clinical Investigation, 2020-01) -
Using structural analysis In Silico to assess the impact of missense variants in MEN1
(Endocrine Society, 2019-09-27)Despite the rapid expansion in recent years of databases reporting either benign or pathogenic genetic variations, the interpretation of novel missense variants remains challenging, particularly for clinical or genetic ... -
CAKUT and autonomic dysfunction caused by acetylcholine receptor mutations
(Cell Press, 2019-12)Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in the first three decades of life, and in utero obstruction to urine flow is a frequent cause of secondary ...
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