Dr Meena Balasubramanian


Clinical Medicine, School of Medicine and Population Health

Senior Clinical Lecturer in Musculoskeletal Genetics

MRC Fellow, University of Sheffield.

Honorary Consultant Clinical Geneticist; Sheffield Children’s 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.

Dr Meena Balasubramanian
Dr Meena Balasubramanian
Profile picture of Dr Meena Balasubramanian
+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 - iicd-om-operational@sheffield.ac.uk

I am a Senior Clinical Lecturer in Musculoskeletal Genetics and experienced Consultant Clinical Geneticist providing Genetics input to Highly specialised Osteogenesis Imperfecta (OI) Service since 2012.

Clinical: I have established Sheffield as an international centre for bone genetics. I set up a national specialist clinic for SATB2 gene patients in Sheffield. Medical and scientific advisory board member for patient support groups: SATB2 Foundation; Brittle Bone Society (BBS); UNIQUE and Scientific Advisory Committee member for The Children’s Hospital Charity.

Innovation: I lead Bone Fragility domain for Musculoskeletal Genomic Clinical Interpretation Partnership (MSK GeCIP): Panelapp expert; I identified a new OI gene (NBAS) published in Bone, 2017; and currently set up my own laboratory working with zebrafish to develop new treatments for patients with NBAS-related disorder

Leadership: I am Research Director for North East and Yorkshire (NEY) Genomic Medicine Service Alliance, NHS England and established the NEY Genomic Research Network at UoS. I co-led Rare Bone Disease-European Reference Network (BOND-ERN) 'Diagnostic Challenges’ working group (2017-21); set out ‘White paper on OI diagnoses which I presented at European Parliament (2018). Elected Consultant council member and Secretary- Clinical Genetics Society, the national body for Clinical Geneticists (2021-to date).

Research: I have published >110 manuscripts in high-impact journals; h-index 19; 2559 Citations; I lead 12 national bone genetics projects & 17 Complementary Analysis Proposals (CAP) in Deciphering Developmental Disorders (DDD) study; written textbook on OI-genomics (2017). Mellanby Centre, UoS Principal Investigator.

Teaching: I am scientific board member for the national Genomics Audit & Research Collaborative set up by trainees in Genetics and genomic counselling and lead the ‘NEY genomic research network’. I provide UoS Medical school teaching on basic genetics, SSC placements, Sheffield Academic Medicine Society supervision and MMI interviews, summative and formative assessments for UoS medical students. I supervise PhD (1), MSc (3); BMedSci (3) at UoS; Faculty, Belgium Rare Bone Symposium; lecture MSc-Genomic Medicine, Endocrinology. Invited to deliver high-impact national and international teaching on bone genetics.


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

10/2012   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.                

06/2004   Diploma in Child Health, Royal College of Paediatrics and Child Health.

06/2001   Bachelor in Medicine and Bachelor in Surgery (MBBS).              

Research interests

My main areas of research currently are in,

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

-Genomic Medicine (Undiagnosed genetic disorders; HNRNPU and ASXL3-related disorder).

-Rare bone genetics

1. NBAS Therapy (as PI, Funded by MRC): During studies to identify genes associated with rare osteogenesis imperfecta (OI) phenotypes, I 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, develop a fish model that accurately mimics human disease and identify potential new treatments. This would be beneficial to patients with both bone and liver manifestations of disease and could inform on a wider front regarding cell membrane trafficking and effects on collagen processing and secretion.

Patients with NBAS are subjected to a lifetime of recurrent fractures, repeated episodes of acute liver failure needing recurrent hospital admissions and immune deficiency. Developing druggable targets towards making this condition better would have a positive impact on quality of life for patients.

My career goal is to become a translational clinician scientist focused on patient-oriented research in bone fragility and establish a dynamic, cutting-edge bone genetics research group within University of Sheffield.

2. Novel gene discovery in OI and understanding disease mechanism for non-collagen OI genes (100,000 Genomes Project)

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 (as Co-I, OsteoStem Study; funded by The Children’s Hospital Charity)

Working alongside Dr Barbaric at School of Biosciences, we are generating pilot data for a MRC grant application for phenotypic assays created to facilitate molecular and cellular characterisation of OI phenotype of individual patients using iPSC cell lines. We hypothesise that the 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. Here, we propose to derive iPSCs from our existing banks of OI patients’ fibroblasts. We will differentiate OI iPSCs to osteoblasts and 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 (as PI, FAME Study; funded by Alexion Pharmaceuticals):

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 (Deciphering Developmental Disorders (DDD) study and 100,000 Genomes Project)

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 syndrome (as PI, funded by The Children’s Hospital Charity)

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. I have published the largest HNRNPU patient cohort (Yates et al., 2017; Durkin et al., 2021; Taylor et al., 2022) and now need to understand underlying disease mechanism and engineer therapeutic interventions for HNRNPU syndrome making use of close links between me (as clinical lead), Professor Stuart Wilson, Professor Ferraiuolo and Dr Seward (molecular) at UoS.

The co-location of this unique team means we could take a world leading position on HNRNPU gene therapy, which could become a model for similar loss-of-function brain disorders and establish Sheffield as a pioneer for this therapeutic approach.

3. ASLX3-related disorder, also referred to as Bainbridge-Ropers syndrome, is a newly described syndrome 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, I have published a patient guide for ASXL3.

Setting up the ASXL3-study:

Ethical approval for the registry and clinic set-up with sample collection is underway.

Investigating ASXL3 mutation cluster & contribution of missense variants:

Disease mechanism is thought to be due to loss-of-function variants but missense ASXL3 variants are picked up with relatively high frequency through WES/WGS studies. I will systematically explore and compare genotypes and phenotypes with special emphasis on ID, cardiac defects in these patients and episignature data to look at disease contribution.

ASXL3 Registry:

Subsequently, the comprehensive, anonymised international dataset will be inputted onto a bespoke web-based registry, designed specifically for ASXL3-related disorder. Families will be provided with the information to sign up to this registry so that they can access more patient-specific information with regards to outlook and prognostication, based on the genotype-phenotype information we collate and will have an annual update reminder to input further clinical information/ new developments so we are able to obtain longitudinal data on this condition and information on natural history for this disorder.

Sample collection:

Skin biopsies will be co-ordinated and arranged, at a time convenient to the patient and families, such as during planned percutaneous gastrostomy insertion which is a common procedure seen in this condition. DNA samples in the form of blood samples will be stored.

Methylation Signature & iPSC Cell Lines:

ASXL3 methylation episignature will be undertaken by generating genome-wide DNA methylation data and employ bioinformatic pipeline to define an ASXL3 specific signature. This signature will enable classification of sequence variants of uncertain significance.

Partnership with National Rare Disease Registration Service, Public Health England:

In partnership with NRDS, I will interrogate the population-based data on rare diseases to obtain data on prevalence of ASXL3-related disorder given use of first line WGS in investigating developmental delay. Under the remit of NHS Digital, there is already precedence for NRDS working with Genomics England to investigate data from National Genomic Research Library (NGRL) which contains all the genomics data from 100,000 Genomes project and NHS WGS service to identify and collate data on ASXL3 variants and correlate with clinical information.


Show: Featured publications All publications

Journal articles


All publications

Journal articles


Conference proceedings papers

  • 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




Key research grants as Lead Investigator:

  1. HNRNPU toward developing gene therapy, The Children’s Hospital Charity, 2022.
  2. Unravelling role of NBAS in skeletal development, MRC, 2021.
  3. Family mapping in HPP study, Alexion. 2021.
  4. High bone mass Osteogenesis Imperfecta Study, Charlie Veale Research Award, 2017.
  5. Assessing the Balance of Cost and Determining the Experiences of Families in Paediatric Osteogenesis Imperfecta Healthcare (ABCD Study), Brittle Bone Society Research Grants, 2017.
  6. Phenotype based assays in Osteogenesis Imperfecta, The Children’s Hospital Charity, Sheffield, 2016.
  7. Digital disease phenotyping in inherited bone fragility disorders, Newlife Foundation For Disabled Children, 2016.
  8. Exploring the functionality of a new gene in bone fragility and its role in autism, The Children’s Hospital Charity, Sheffield, 2016.
  9. Exome sequencing in Osteogenesis Imperfecta, The Children’s Hospital Charity, Sheffield, 2015.
  10. Identification of novel phenotypes in a cohort of children with bone fragility and autism, Newlife Foundation for Disabled Children, 2015.
  11. Commitment from Genzyme for high throughput RNA sequencing and TGF-B antibody work-up in cultured fibroblasts from patients with Osteogenesis Imperfecta to identify novel pathways for diagnosis and intervention, 2015.
  12. In-depth phenotyping including studying skin biopsy findings in Osteogenesis Imperfecta, NIHR Rare Disease Translational Research Collaboration, 2014.
  13. NIHR Research Capacity Funding Award- 2014/2015, 2014.
  14. Sheffield Children's NHS Foundation Trust: Academic PA’s, 2014-2016.
  15. Research Capacity Funding from Sheffield Children’s NHS Foundation Trust, 2014.
  16. Novel mechanism leading to Osteogenesis Imperfecta and Type V OI genotype study under the auspices of ‘Deciphering Developmental Disorders' (DDD), Sanger Institute, Wellcome Trust in Cambridge.
  17. 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).

2. 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

I have built a research group comprising doctors & allied health colleagues (lab & genetic counsellors) with a global reputation through publications & presentations in international meetings. I have supervised my group in research outputs (Brueton Prize) & first-author publications in high impact journals like JMedGenet, ClinGenet, HumMut (28 so far). I have 4 non-Genetics trainees on secondment, involved in research projects.

Trainees (Genetics, Neonatal, Neurology, Dental) from other centres have sought my supervision; I supervise 5 non-Sheffield trainees with DDD CAP studies.

My teaching interests are mainly in supervising undergraduate and postgraduate students in genomic medicine projects. I am currently supervising PhD (1 with Insigneo), MSc (2), BMedSci students; supervising applications for PhD/ MD projects-3 (2016-17). I provide supervision to DClinSci (2020-), University of Manchester.

SSC Student Placements: 2/year

I also provide clinical supervision to 2 Genetics Speciality trainees. I undertake STEPP teaching for Paediatric trainees. I am one of two convenors for RCPCH Genetics session (2015-date).

I am an invited reviewer for several genomic medicine and bone genetics manuscripts (2-3/week) & grant review (MRC, Temple Foundation; ESPE; Wellcome) (2014-date).

PhD applications invited.

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.
  • 2017-20: BOND-ERN WG member: ‘Research’, 'Education', ‘Clinical Guidelines’.
  • 2020- : Participant in EuRR Bone Registry as medical member.


  • I am one of two NHS Genomic Medicine Service Alliance North East Yorkshire (NEY) Research Collaborative representing our region on national genomics research board; in 2021 I produced a capacity statement & strategy document for delivering mainstream genomics research for NHS England (2020- to date).
  • Elected representative of national constituent body, Clinical Genetics Society 2017- 2021. As CGS Council Consultant member, I led a working group & wrote National job plan document for Consultant Geneticists for NHS England service specification for Clinical Genetics Services submitted to Clinical Reference Group.
  • GeCIP sub-domain lead for Paediatric Bone Fragility and Metabolic Bone Disease under the Musculoskeletal theme GeCIP (Genomic Clinical Interpretation Partnership) for the 100,000 genomes project- 2016- to date.
  • Research lead for NIHR portfolio & non-portfolio research delivery for Sheffield Genetics (2020- to date).

Patient support groups Medical Advisory Board (MAB)

  • Medical Advisory Board Member, Brittle Bone Society.
  • Medical and Scientific Advisory Board Member, SATB2 international support group.
  • 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.

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- ERF, IQSEC2, HNRNPU, ASXL3, SIN3A; 16p11.3 & 2q33 deletion syndrome (https://www.rarechromo.org/disorder-guides/)