Research Interests:
Research Interests:
Research Interests:
Routine pregnancy screening (e.g. ultrasound scan) may lead unexpectedly to the identification of an underlying renal problem whose aetiology may not be apparent immediately. It is important to recognize genetic causes so that associated... more
Routine pregnancy screening (e.g. ultrasound scan) may lead unexpectedly to the identification of an underlying renal problem whose aetiology may not be apparent immediately. It is important to recognize genetic causes so that associated problems in other organs can be anticipated and the recurrence risk for future pregnancies established. Specific diagnosis at a cytogenetic or molecular level may be essential if the options of early prenatal diagnosis or pre-implantation genetic diagnosis are to be available to the couple in future pregnancies. This chapter discusses the topics of antenatal screening, prenatal diagnosis (including invasive and non-invasive diagnosis and counselling) and intervention, and pre-implantation genetic diagnosis.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Mutations in more than 250 genes are implicated in inherited retinal dystrophy; the encoded proteins are involved in a broad spectrum of pathways. The presence of unsolved families after highly parallel sequencing strategies suggests that... more
Mutations in more than 250 genes are implicated in inherited retinal dystrophy; the encoded proteins are involved in a broad spectrum of pathways. The presence of unsolved families after highly parallel sequencing strategies suggests that further genes remain to be identified. Whole-exome and -genome sequencing studies employed here in large cohorts of affected individuals revealed biallelic mutations in ARHGEF18 in three such individuals. ARHGEF18 encodes ARHGEF18, a guanine nucleotide exchange factor that activates RHOA, a small GTPase protein that is a key component of tight junctions and adherens junctions. This biological pathway is known to be important for retinal development and function, as mutation of CRB1, encoding another component, causes retinal dystrophy. The retinal structure in individuals with ARHGEF18 mutations resembled that seen in subjects with CRB1 mutations. Five mutations were found on six alleles in the three individuals: c.808A>G (p.Thr270Ala), c.1617+5...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Routine pregnancy screening (e.g. ultrasound scan) may lead unexpectedly to the identification of an underlying renal problem whose aetiology may not be apparent immediately. It is important to recognize genetic causes so that associated... more
Routine pregnancy screening (e.g. ultrasound scan) may lead unexpectedly to the identification of an underlying renal problem whose aetiology may not be apparent immediately. It is important to recognize genetic causes so that associated problems in other organs can be anticipated and the recurrence risk for future pregnancies established. Specific diagnosis at a cytogenetic or molecular level may be essential if the options of early prenatal diagnosis or pre-implantation genetic diagnosis are to be available to the couple in future pregnancies. This chapter discusses the topics of antenatal screening, prenatal diagnosis (including invasive and non-invasive diagnosis and counselling) and intervention, and pre-implantation genetic diagnosis.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The increasing availability of genetic tests is transforming health care. Patients can benefit from earlier, more precise diagnosis and sometimes tailor-made treatment; their relatives can be offered pre-symptomatic, predictive tests and... more
The increasing availability of genetic tests is transforming health care. Patients can benefit from earlier, more precise diagnosis and sometimes tailor-made treatment; their relatives can be offered pre-symptomatic, predictive tests and carrier tests. Physicians must balance confidentiality with duty to other individuals, and are responsible for using genetic tests for the benefit of patients in an ethical way. An offer of testing must balance potential additional benefit from potential downsides of testing including psychological effects, risk of error, continuing uncertainty, and cost. The ability to do multiple tests on many genes, even to sequence the whole genome, is rapidly approaching, and mainstreaming of tests means that geneticists are not necessarily involved. Further work and thinking needs to inform medical ethics in this area.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Genetics, Biology, Adolescent, Intellectual Disability, Medicine, and 15 moreHumans, Child, Mutation, Female, Male, Developmental disabilities, Phenotype, Clinical Sciences, Medicine and Health Sciences, Congenital Hypothyroidism, Medical Clinic, Sotos syndrome, Child preschool, Chromosome deletion, and Craniofacial Abnormalities
Research Interests:
Research Interests:
Research Interests:
Genetic testing for pathogenic COL4A3–5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate... more
Genetic testing for pathogenic COL4A3–5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate genetic testing for persistent hematuria, even when a heterozygous pathogenic COL4A3 or COL4A4 is suspected, and cascade testing of their first-degree family members because of their risk of impaired kidney function. The experts recommend too that COL4A3 or COL4A4 heterozygotes do not act as kidney donors. Testing for variants in the COL4A3–COL4A5 genes should also be performed for persistent proteinuria and steroid-resistant nephrotic syndrome due to suspected inherited FSGS and for familial IgA glomerulonephritis and kidney failure of unknown cause.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Genetics, Human Genetics, Human Development, Biology, Forecasting, and 15 moreRisk assessment, Medicine, Pregnancy, Humans, Genetic Testing, Female, In Vitro Fertilization, Aneuploidy, Preimplantation genetic diagnosis, Ethical Issues, Genetic Disorder, Prenatal Diagnosis, Risk Assessment, Oocytes, and Embryos
Research Interests:
1. Introduction to clinical genetics 2. Renal function and management of renal disease 3. Renal development 4. Kidney and lower urinary tract malformations 5. Urinary tract defects and chromosomal disorders 6. Dysmorphic syndromes with... more
1. Introduction to clinical genetics 2. Renal function and management of renal disease 3. Renal development 4. Kidney and lower urinary tract malformations 5. Urinary tract defects and chromosomal disorders 6. Dysmorphic syndromes with renal involvement 7. Primary hereditary nephropathies 8. Alport Syndrome 9. Autosomal dominant polycystic kidney disease 10. Autosomal recessive polycystic kidney disease 11. Cystic renal diseases 12. Primary inherited metabolic diseases of the kidney 13. Genetics of stone forming diseases 14. Disorders of tubular transport 15. Tuberous Sclerosis complex 16. Neurofibromatosis 17. The Bardet-Biedl and Alstrom syndromes 18. Genetic syndromes with a renal component 19. The genetics of glomerulonephritis and systemic disorders affecting the kidney 20. Wilms tumour and the Wilms tumour predisposition syndromes 21. Von Hippel-Lindau disease 22. Inherited predispositions to kidney cancer 23. Gene therapy in renal disease 24. Gene therapy for renal cancer
Research Interests:
Research Interests:
Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding... more
Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understan...
Research Interests:
Study question Does conception by Preimplantation Genetic Testing (PGT-M, PGT-SR) adversely affect health outcomes in children born through this assisted reproductive technique? Summary answer No significant difference was noted in the... more
Study question Does conception by Preimplantation Genetic Testing (PGT-M, PGT-SR) adversely affect health outcomes in children born through this assisted reproductive technique? Summary answer No significant difference was noted in the rate of congenital malformations in children born after PGT-M and PGT-SR compared with IVF-ICSI children. What is known already It is already known that the risk of congenital anomalies in IVF-ICSI pregnancies is higher when compared with pregnancies conceived naturally. Study design, size, duration This is a prospective study on 747 children born between December 1999 and July 2016 after a cycle of PGT-M or PGT-SR (IVF +/- ICSI + embryo biopsy) performed at a single London reproductive centre. PGT-A is not performed in the Centre, so pregnancy outcomes in this group are not relevant. The children were examined at birth, at 12 and 24 months of age and the data collected in three questionnaires. Participants/materials, setting, methods 747 PGT-M and PG...