Dr Meena Balasubramanian


Clinical Medicine, School of Medicine and Population Health

Senior Clinical Lecturer in Musculoskeletal Genetics

Clinical Director for Research, Sheffield Childrens Hospital NHS Foundation Trust.

Founding Director, SCYPHeR (Sheffield Children and Young People Health Research) Initiative.

Honorary Consultant Clinical Geneticist; Sheffield Childrens NHS Foundation Trust.

Research Director, NHS North East and Yorkshire Genomic Medicine Service Alliance.

Lead Consultant Bone Geneticist for the nationally-commissioned Osteogenesis Imperfecta service in England.

MED - Meena Balasubramanian
Dr Meena Balasubramanian
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+44 114 215 9008
+44 114 271 7025 (Secretary)

Full contact details

Dr Meena Balasubramanian
Clinical Medicine, School of Medicine and Population Health
Firth Court
Western Bank
S10 2TN

For enquiries please contact - ClinMed-Operational@sheffield.ac.uk

Rare diseases affect over 3.5 million people in the UK and recent medical advances have provided the means to generate diagnoses for several rare diseases that have been studied to-date but have no treatment. Importantly, a large proportion of these diseases are caused by specific alterations in the genetic building blocks or DNA of affected patients. I am a Clinician Scientist and Academic Clinical Geneticist who combines clinical insights into rare diseases with excellent science on in vivo and in vitro modelling, capitalising on key strengths I have gained through my career to-date, providing a direct link to translational medicine and the independence to pursue my vision of transforming care provided for rare disease patients.

My current research programme have the following themes:

  1. Enabling early confirmatory diagnosis through mining genomics data and functional characterisation of novel rare disease genes.
  2. Understanding disease mechanism through cell-based and animal modelling.
  3. Natural history studies with the focus on pulling together ‘trial-ready’ cohorts of rare disease patients with emphasis on advanced gene-directed therapies.

I hold a joint position with Sheffield Children’s Hospital which is only one of three dedicated children’s hospital in the UK. I care for children and adults with rare genetic disorders. I am also the Research Director for Sheffield Children’s Hospital.

Current PhD Opportunities:

PhD applications invited.


06/2023 Fellow of Health Education Academy, Advance HE (FHEA)

10/2016   Fellow of RCPCH: Nominated by Royal College of Paediatric and Child Health (FRCPCH)

12/2012   MD (Doctor in Medicine), Dept of Human Metabolism, University of Sheffield on Osteogenesis Imperfecta

07/2007   Member of Royal College of Paediatric and Child Health (MRCPCH)      

06/2004   Diploma in Child Health, Royal College of Paediatrics and Child Health (DCH)

06/2002   Bachelor in Medicine and Bachelor in Surgery (MBBS)            

Research interests

My group’s main areas of research currently are in,

Rare bone genetics (NBAS therapy; Novel gene discovery in OI; OI gene therapy; Hypophosphatasia).

Rare neurodevelopmental disorders (Undiagnosed genetic disorders; HNRNPU and ASXL3-related disorder).

Rare bone genetics

1. NBAS Therapy: During studies to identify genes associated with rare osteogenesis imperfecta (OI) phenotypes, we discovered that the same mutations in NBAS (Neuroblastoma Amplified Sequence) known to be associated with acute liver failure in infants were responsible for skeletal abnormalities in patients with OI. This work was published as a novel cause of bone fragility. This discovery provided me the opportunity to use tractable animal (zebrafish) research to advance understanding of the mechanisms by which NBAS exerts its effects, having generated zebrafish models that accurately mimic human disease in order to identify potential new treatments.

2. Novel gene discovery in OI and understanding disease mechanism for non-collagen OI genes: This is a long-standing research interest of mine focused on mining genomics data for new gene discovery working alongside diagnostic colleagues from 100,000 Genomes project for which I lead the bone fragility domain as GeCIP lead and NHS whole genome sequencing. This has led me to identify novel OI genes which are being worked up. An additional area is genes linking brain and bone disease such as Sodium Channelopathies, spermine synthase and SETD5 which I am exploring the causal link and why these disorders cause a bone phenotype.

3. OI Gene therapy: We are working towards developing phenotypic assays to facilitate molecular and cellular characterisation of OI phenotype using iPSC cell lines. We hypothesise that access to disease-relevant cells with patient-specific variants will provide the most representative models of OI, thus allowing us to set up reliable assays for therapeutic discovery. We are deriving iPSCs from our existing banks of OI patients’ fibroblasts and differentiating these into osteoblasts. We plan to set up a phenotypic assay as a proof-of-principle for future high-throughput drug discovery efforts and in-depth mechanistic studies.

4. Family mapping in Hypophosphatasia (FAME Study): The aim of this study is to detect additional symptomatic and asymptomatic HPP patients within affected families, in order to establish a cohort of HPP patients using family mapping and predictive genotyping approach. In addition, we also want to examine the relationship between a pathogenic variant in ALPL and musculoskeletal symptoms and other aspects of general health status.

Genomic Medicine

1. Undiagnosed Genetic Disorders and functional studies This involves mining genomics data for rare phenotypic presentations and discovering candidate genes for novel neurodevelopmental and congenital disorders and identifying additional international patients through interrogation of worldwide genomic datasets using Genematcher and Matchmaker exchange programmes; undertaking functional studies for publication of a novel genes.

2. HNRNPU-related disorder HNRNPU-related disorder is a neurodevelopmental disorder characterised by heterozygous, de novo, loss-of-function variants in HNRNPU. Patients with pathogenic variants in HNRNPU present with seizures, global developmental delay, early onset epilepsy, hypotonia, autistic features, and a variety of anatomical abnormalities and intellectual disability. My group has published the largest HNRNPU patient cohort (Yates et al., 2017; Durkin et al., 2021; Taylor et al., 2022) and now working to understand underlying disease mechanism and engineer therapeutic interventions for HNRNPU syndrome. Knowledge gained from this can act as a model for similar loss-of-function RNDDs and establish Sheffield as a pioneer for this therapeutic approach. We now have a natural history study focused on longitudinal clinical data and sample collection for HNRNPU. We also published a Genereview chapter on clinical diagnosis and management of HNRNPU (Balasubramanian., 2022). Working with ‘Unique’ rare disease patient support group, we have published a patient guide for HNRNPU-related disorder.

3. ASLX3-related disorder, also referred to as Bainbridge-Ropers syndrome, is characterised by developmental delay and intellectual disability caused by heterozygous, de novo pathogenic variants in ASXL3 (Additional Sex Combs-Like 3). Over the last 5 years, my group has published most of the literature on this condition (Balasubramanian et al., 2017; Myers et al., 2018; Schirwani et al., 2019; Schirwani et al., 2021) and published a Genereview chapter on clinical diagnosis and management of the condition (Balasubramanian., 2020). Working with ‘Unique’ rare disease patient support group, we have published a patient guide for ASXL3. We now have a natural history study focused on longitudinal clinical data and sample collection for ASXL3.


Show: Featured publications All publications

Journal articles


All publications

Journal articles


Conference proceedings papers

  • Godfrey M, Levy M, Leonardi E, Campbell C, Demain L, Jenkinson S, Hilton S, Almoguera Castillo B, Balasubramanian M, Bijlsma EK , Burkitt-Wright E et al (2024) CHD8 missense variants cause a variable neurodevelopmental disorder with incomplete penetrance. EUROPEAN JOURNAL OF HUMAN GENETICS, Vol. 32 (pp 721-721) RIS download Bibtex download
  • Rots D, Yamada A, Foroutan A, McCon-Key H, Kerkhof J, Alders M, Maystadt I, Holden S, Balasubramanian M, Merla G , San-Ten G et al (2023) Systematic evaluation of EHMT1 protein altering variants uncovers unexpected insights on EHMT1 functions and Kleefstra syndrome pathogenesis. EUROPEAN JOURNAL OF HUMAN GENETICS, Vol. 31 (pp 456-457) RIS download Bibtex download
  • Blaschitz A, Rao AA, Castiglioni C & Balasubramanian M (2023) Heterozygous mutations in SETD5 are associated with bone fragility. HORMONE RESEARCH IN PAEDIATRICS, Vol. 96 (pp 479-480) RIS download Bibtex download
  • Griffin M, Balasubramanian M, Blyth M, Dixit A, Turnpenny PD & Suri M (2022) Deep phenotyping of biallelic HACE1 variants. EUROPEAN JOURNAL OF HUMAN GENETICS, Vol. 30(SUPPL 1) (pp 280-281) RIS download Bibtex download
  • Quarrell OW, Rautengarten C, Stals K, Caswell R, De Franco E, Baple E, Burgess N, Jokhi R, Hazelwood JL, Offiah AC , Ebert B et al (2019) Report of a novel variant causing a schneckenbecken-like dysplasia. European Journal of Human Genetics, Vol. 27 (pp 1298-1299). Gothenburg, Sweden, 15 June 2019 - 18 June 2019. View this article in WRRO RIS download Bibtex download
  • Kanani F, Titheradge H, Cooper N, Elmslie F, Lees M, Juusola J, Pisani L, Mignot C, Valence S, Keren B , Guella I et al (2019) De novo, heterozygous missense variants in YWHAG as a novel cause of developmental and epileptic encephalopathy. European Journal of Human Genetics, Vol. 27(Supplement 2) (pp 1471-1472). Gothenburg, Sweden, 15 June 2019 - 18 June 2019. View this article in WRRO RIS download Bibtex download
  • Calpena E, Cuellar A, Bala K, Swagemakers SMA, Koelling N, McGowan SJ, Balasubramanian M, Morton JEV, Weber A, Wilson LC , Johnson D et al (2019) BMP2 or not BMP2? A SMAD6-related question in craniosynostosis. EUROPEAN JOURNAL OF HUMAN GENETICS, Vol. 27 (pp 1277-1278) RIS download Bibtex download
  • Peacock A, Offiah AC, Balasubramanian M, Bishop N & Arundel P (2019) Radiographic evidence of zoledronic acid given during pregnancy - a case report. Bone Abstracts, Vol. 7. Salzburg, Austria, 22 June 2019 - 25 June 2019. View this article in WRRO RIS download Bibtex download
  • Low T, Kostakis A & Balasubramanian M (2018) Compound heterozygous variants in IFT140 as a cause of non-syndromic Retinitis Pigmentosa. EUROPEAN JOURNAL OF HUMAN GENETICS, Vol. 26 (pp 851-851) View this article in WRRO RIS download Bibtex download
  • Zarate YA, Gambello M, Pandya A, Saenz M, Siu VM, Ray J, Sellars E, Sun A, Smith W, Robin NH , Picker J et al (2018) PHENOTYPE AND NATURAL HISTORY IN 49 INDIVIDUALS WITH SATB2- ASSOCIATED SYNDROME. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, Vol. 176(6) (pp 1526-1527) View this article in WRRO RIS download Bibtex download
  • Balasubramanian M, Hurst J, DeVile C, Bishop N, Arundel P, Offiah A, Pollitt R, Hughes D, Longman D, Caceres J & Skerry T (2017) NBAS variants causing a novel form of inherited bone fragility. Bone Abstracts, Vol. 6(2017). Bristol, UK, 10 June 2017 - 13 June 2017. View this article in WRRO RIS download Bibtex download
  • He Y, Yalcin E, Balasubramanian M, O'Reilly R, Bruckner-Tuderman L & Has C (2015) Molecular mechanism underlying interstitial lung disease, nephrotic syndrome and epidermolysis bullosa. JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol. 135 (pp S59-S59) RIS download Bibtex download
  • Balasubramanian M, Bourke S, Crawford N & Cohen M (2011) Referral to Clinical Genetics following post modem examination in foetal losses. JOURNAL OF MEDICAL GENETICS, Vol. 48 (pp S58-S58) RIS download Bibtex download
  • Balasubramanian M, Johnson DS & Sobey GJ (2009) Blue rubber bleb naevus syndrome- severe presentation in a neonate. JOURNAL OF MEDICAL GENETICS, Vol. 46 (pp S60-S60) RIS download Bibtex download
  • Balasubramanian M & Johnson DS (2009) Previously unreported feature in IMAGe Syndrome: Case discussion and review of published literature. JOURNAL OF MEDICAL GENETICS, Vol. 46 (pp S60-S60) RIS download Bibtex download
  • Balasubramanian M & Collins AL (2009) Audit on Genetics Ward Round- Wessex Experience. JOURNAL OF MEDICAL GENETICS, Vol. 46 (pp S58-S58) RIS download Bibtex download
  • Balasubramanian M & Quarrell OW (2008) Update of a unique case report by Tandon et al- Clefting with irido-retinochoroidal coloboma and skeletal abnormalities. JOURNAL OF MEDICAL GENETICS, Vol. 45 (pp S37-S37) RIS download Bibtex download
  • Balasubramanian M & Johnson DS (2008) Cutis aplasia, cardiac anomaly and abnormalities of portal vasculature: varying presentation in Adams Oliver Syndrome. JOURNAL OF MEDICAL GENETICS, Vol. 45 (pp S38-S38) RIS download Bibtex download
  • Balasubramanian M & Collins A (2008) Aplasia cutis congenita, terminal limb defects and bilateral closed lip schizencephaly- a variant of Adams-Oliver Syndrome. JOURNAL OF MEDICAL GENETICS, Vol. 45 (pp S37-S37) RIS download Bibtex download
  • Vijayavel K & Balasubramanian MP (2006) Fluctuations of biochemical constituents and marker enzymes as a consequence of naphthalene toxicity in the edible estuarine crab Scylla serrata. Ecotoxicology and Environmental Safety, Vol. 63(1) (pp 141-147) RIS download Bibtex download



Research group

My group is working on two main research areas: Rare Bone Disorders and Rare Neurodevelopmental Disorders

1. Rare Bone Disorders (RBD)

I am working on two RBDs: Osteogenesis Imperfecta (OI) and Hypophosphatasia (HPP). I am currently pursuing an MRC Fellowship on developing zebrafish disease models for bone fragility and developing targets for therapeutic intervention having set up ‘Balasubramanian lab’ at Bateson Centre, University of Sheffield.

I lead inter-disciplinary bone genetics research: deep phenotyping (first Musculoskeletal NIHR Rare Disease Translational Research collaboration grant), fracture risk prediction models; genomics in OI and awarded grants by Brittle Bone Society in their first ever research call to study OI health economics and patient diagnostic journey and BRONE Study studying brain and bone association.

2. Rare Neurodevelopmental Disorders (RNDDs)

In the area of paediatric genomic medicine, my research is focused on genotype-phenotype correlation in newly identified genes from next generation sequencing studies such as Deciphering Developmental Disorders (DDD) study and the Genomics England, 100,000 Genomes Project. I am considered one of the world-leading experts on these disorders and have published national and international guidelines on diagnosis, management and ongoing surveillance for such disorders including ASXL3-related disorder, HNRNPU-related neurodevelopmental disorder, and SIN3A-related disorder. I am also working on developing gene therapy for rare neurodevelopmental disorders (RNDDs) and recently secured funding from The Children’s Hospital Charity and LifeArc to work on preliminary data collection for this proposal.

PhD Students:

2023               PhD (N Supari), Variants of uncertain significance: OI
2023               PhD (D Aiyedun), HNRNPU-related disorder
2023               PhD (N Kelly), Gene therapy in OI (MRC DiMEN)
2022               MD (E Woods), ASXL3-related syndrome
2020               PhD (T Cebe), Collagen orientation in OI


Key Research Grants as Lead Investigator:

  1. SCYPHeR Initiative, UoS Knowledge Exchange Funding, 2023
  2. SkelFish Study, The Children’s Hospital Charity, 2023
  3. HNRNPU toward developing gene therapy, The Children’s Hospital Charity and LifeArc Pathfinder Scheme, 2022
  4. Unravelling role of NBAS in skeletal development, MRC, 2021
  5. Family mapping in HPP study, Alexion Pharmaceuticals, 2021
  6. High bone mass Osteogenesis Imperfecta Study, Charlie Veale Research Award, 2017
  7. Assessing the Balance of Cost and Determining the Experiences of Families in Paediatric Osteogenesis Imperfecta Healthcare (ABCD Study), Brittle Bone Society Research Grants, 2017

Complementary Analyses Proposals (Deciphering Developmental Disorders Study- Sanger Institute, Cambridge) https://www.deciphergenomics.org/ddd/complementary-analyses.
- XPO1 as a novel cause of congenital anomaly disorder including intellectual disability [#356]
SP4 as a novel cause of congenital anomaly disorder including intellectual disability [#346]
TAOK1-related neurodevelopmental disorder [#347]
- Genotype-phenotype correlation in USP7 (Hao-Fountain Syndrome) [#336]
ZFHX4-Related Developmental Disorder [#337]
SIN3A: Genotype-phenotype correlation [#282]
- Expanding the phenotype of TAB2 variants [#279]
- Genotype-phenotype correlation in NSDHL [#268]
- Genotype-phenotype correlation in YWHAG [#267]
- Study of patients with Joubert syndrome and CC2D2A variants [#263]
- Expansion of the movement disorder phenotype in SCN2A-related disease [#262]
- Study of patients with MAN1B1 mutations [#249]
- Genotype-phenotype correlation in ASXL3 (Bainbridge-Ropers syndrome) [#130]
- Genotype-phenotype correlation in NBAS [#143]
- Cole-Carpenter syndrome CRTAP [#96]
- Novel mechanisms causing Osteogenesis Imperfecta [#12]
- Hypophosphatasia and ALPL mutations [#213]
- Genotype-phenotype correlation in ATP1A3 [#135]
- Genotype-phenotype correlation in HNRNPU [#204]
- Genotype-phenotype correlation in IQSEC2 [#267]
Genotype-phenotype correlation in VLDLR [#2197]
Genotype-phenotype correlation in SRPX2 [#221]
- Genotype-phenotype correlation in LAMP2 [#228]


  1. Osteostem study (CI: Dr Barbaric, University of Sheffield).
  2. Sensory profiles in genetic syndromes associated with autism (CI: Dr Freeth, University of Sheffield).
  3. Sheffield PI for PregCare Study (CI: Prof Goriely and Prof Wilkie, University of Oxford); Additional findings study (CI: Prof Chitty and Dr Hill, UCL); Patient experience in WGS (CI: Dr Lewis, UCL); Splicing study (CI: Prof Baralle, University of Southampton).
Teaching interests

Postgraduate University Courses/ Teaching:

MSc Teaching:

  1. MMedSci Advance Clinical Practice: Genetics session
  2. MSc Workplace modules (MED680)
  3. MSc Endocrinology lecture on rare disease genetics
  4. MSc in Human and Molecular Genetics (Module on Genetics in Human Disease)
  5. University of Sheffield MSc Genomic Medicine lectures (MED670)

MSc Project Supervision:

2023               MSc Molecular Biology and Biotechnology
2023               MSc Neuroscience and Advanced Therapies
2023               MSc Scientist Training Programme
2022               Summer Internship, University of Applied Sciences in Weihenstephan-Triesdorf, Freising, Germany
2020               MSc Genomic Medicine
2020               MSc Genomic Medicine, UCL

Undergraduate Teaching:

I am the MBChB Medical Careers Theme Lead (Aug’23 onwards). In this role, I am providing strategic oversight to develop the careers strategy for AUME and ensure this aligns with the University pillars. I am leading on a project embedding mySkills into the MBChB curriculum and working with the AUME Directors and core group to ensure career theme is implemented consistently

My formal teaching also includes,

  1. 1st and 3rd year University of Sheffield medical students’ Paediatric lectures
  2. ILA Facilitator, Phase 1 MBChB
  3. I participate in MBChB formative and summative assessments and clinic teaching.
  4. I participate in the Medical Student interviews (MMI)
  5. Assessor for SSC History of Medicine
  6. I contribute regularly to Phase 2a MBChB SBA question banks
  7. 3-week Clinical Genetics placements for MBChB students with excellent feedback with most returning to do projects with me.
  8. SSC placements and BSc Intercalating student supervision

Specialist Courses:

  1. I deliver at least 6-7 invited lectures every year for post-graduate students/ doctors on Osteogenesis Imperfecta and rare bone genetics (National Genetics Trainee Day/ All Wales Genetics Service Training Day/ Pan Thames Skeletal Dysplasia Teaching/ Yorkshire and Humber Teaching Day to name a few)
  2. I provide national and international teaching for Genetics trainees on ‘Osteogenesis Imperfecta’ and ‘Atypical Bone Fragility’ (Belgian Rheumatology Association)
  3. I provide post-graduate genetics teaching to paediatric trainees (STEPP teaching) for Yorkshire and Humber Deanery and invited by several sub-specialities to give lectures on their organised study days on Genomic medicine (this includes Paediatric Endocrinology, Ophthalmology, and Paediatrics in peripheral hospitals)
  4. I am actively involved in teaching Paediatric trainees for MRCPCH and DCH examinations
  5. Deliver lectures in India at the International Birth Defects Conference, JSS University, Mysuru and Apollo Institute, New Delhi
Professional activities and memberships


  • Rare Bone Disease European Reference Network Working Group 1 (Diagnostic Challenges) Co-leader (BOND ERN)- 2017-2021. Steering group member for BOND ERN- 2017-2021
  • 2018: I set out & presented White Paper on current status of OI diagnosis & improving patient pathways at European Parliament


  • Clinical Genetics Society (UK) - Secretary
  • British Society of Genomic Medicine
  • Skeletal Dysplasia Group
  • Royal College of Paediatrics and Child Health
  • General Medical Council

Patient support groups Medical Advisory Board (MAB)

  • Medical and Scientific Advisory Board Member, HNRNP international support group (2022-)
  • Medical Advisory Board Member, Brittle Bone Society (2019-)
  • Scientific Advisory Committee member, Sheffield Children's Hospital Charity (2018-)

I set up and lead the ‘North East and Yorkshire Genomic Research Network’ with inaugural meeting in June 22 to encourage genomics research across the NEY region in collaboration with academic universities (University of Newcastle, Sheffield, Leeds, York and Bradford), Genomic Laboratory Hubs and Genomics Medicine Service Alliance working with Genomics England.

NHS Genomic Medicine Service Alliance North East Yorkshire (NEY) Research Director (2020-) The NHS Genomic Medicine Service (GMS) Research Collaborative has been brought together as part of the NHS Long Term Plan aim to support research and development by facilitating genomic research on a national scale and ensure alignment with national research aims to deliver better outcomes for patients both now and in the future. The NHS GMS Research Collaborative is a partnership between the NHS GMS, Genomics England and the National Institute of Health Research (NIHR).

A key aim of the NHS GMS is to support research and development, including the development of a single genomic knowledgebase to allow research on a national scale, and ensure alignment with national research aims. The NHS GMS Research Collaborative provides a forum through which NHS England and NHS Improvement, NHS Genomic Laboratory Hubs, NHS GMS Alliances, Genomics England and the National Institute for Health Research work in partnership to facilitate high-quality genomic research on a national scale.

I am the NEY NHS GMSA Research Director with my role focused on promoting genomic research in our region across the academic institutions in the region (University of Newcastle, Leeds, Sheffield, York and Bradford) and NHS organisations across the region.

Leadership Activities

2023 - Clinical Director of Research, SCH
2023 - Founding Director, Sheffield Children & Young People Health Research (SCYPHeR) Initiative between Sheffield Children’s Hospital, Sheffield Hallam University and  University of Sheffield
2022 - Impact Lead, Division of Clinical Medicine, UoS
2023 - REF Reviewer, Oncology & Metabolism, UoS           -
2022 - Athena SWAN SAT Committee Member, Athena SWAN Organisation and Culture sub-group Committee Member
2021-2023 - Research Director, NHS North East Yorkshire (NEY),Genomic Medicine Service Alliance

Patient information leaflets

2020-21: Genetics in OI; pregnancy in OI leaflets

2019-20: Brittle Bone Society: Genetics Podcast; public lectures on autism

2013-20: Unique guides for these genetic disorders- ERFIQSEC2HNRNPUASXL3SIN3A16p11.3 & 2q33 deletion syndrome (https://www.rarechromo.org/disorder-guides/); NORD guides for HNRNPU, ASXL3