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Escande-Beillard, N., A. Loh, S. N. Saleem, K. Kanata, Y. Hashimoto, U. Altunoglu, A. Metoska, J. Grandjean, F. M. Ng, O. Pomp, et al., "Loss of PYCR2 Causes Neurodegeneration by Increasing Cerebral Glycine Levels via SHMT2.", Neuron, vol. 107, issue 1, pp. 82-94.e6, 2020. Abstract

Patients lacking PYCR2, a mitochondrial enzyme that synthesizes proline, display postnatal degenerative microcephaly with hypomyelination. Here we report the crystal structure of the PYCR2 apo-enzyme and show that a novel germline p.Gly249Val mutation lies at the dimer interface and lowers its enzymatic activity. We find that knocking out Pycr2 in mice phenocopies the human disorder and depletes PYCR1 levels in neural lineages. In situ quantification of neurotransmitters in the brains of PYCR2 mutant mice and patients revealed a signature of encephalopathy driven by excessive cerebral glycine. Mechanistically, we demonstrate that loss of PYCR2 upregulates SHMT2, which is responsible for glycine synthesis. This hyperglycemia could be partially reversed by SHMT2 knockdown, which rescued the axonal beading and neurite lengths of cultured Pycr2 knockout neurons. Our findings identify the glycine metabolic pathway as a possible intervention point to alleviate the neurological symptoms of PYCR2-mutant patients.

Wade, A. D., R. Beckett, G. Conlogue, G. Garvin, S. Saleem, G. Natale, D. Caramella, and A. Nelson, "Diagnosis by consensus: A case study in the importance of interdisciplinary interpretation of mummified remains.", International journal of paleopathology, vol. 24, issue March, pp. 144-153, 2018 Oct 30, 2019. Abstract

OBJECTIVE: The goal of this study is to demonstrate the need for interdisciplinary consensus and inclusion of mummy radiology specialists in analyses of mummified remains.

MATERIALS: This study uses paleoimaging data for an ancient Egyptian mummy at the Museum of Human Anatomy "Filippo Civinini".

METHODS: This study demonstrates the benefit of evaluation of mummified remains in a multi-disciplinary interpretive team.

RESULTS: The authors propose a diagnosis of DISH, additional signs of undifferentiated spondyloarthropathy, and lumbarisation of S1.

CONCLUSIONS: The process of diagnosis by consensus is essential to the analysis of mummified remains, which are complexly altered through natural and anthropogenic processes in the millennia subsequent to the individual's death.

SIGNIFICANCE: Mummy paleoimaging and paleopathology lacks a unifying set of standards. We present an example of the value to be found in the multi-disciplinary diagnosis by consensus approach.

LIMITATIONS: We discuss numerous challenges to accurate and meaningful interpretation that radiography of mummified remains pose.

SUGGESTIONS FOR FURTHER RESEARCH: While the authors do not seek to impose any single set of standards, we do recommend a larger discussion on the topic of (culture-specific) standardisation in mummy paleoimaging and paleopathology. We further recommend the development of an international, multi-disciplinary panel of paleoimaging interpreters.

Nabhan, M. M., N. Elkhateeb, D. A. Braun, S. Eun, S. N. Saleem, H. Y. Gee, F. Hildebrandt, and N. A. Soliman, "Cystic kidneys in fetal Walker–Warburg syndrome with POMT2 mutation: Intrafamilial phenotypic variability in four siblings and review of literature", ة American Journal of Medical Genetics Part A, vol. 173, issue 10, pp. 2697-2702, 2017.
Wade, A. D., R. Beckett, G. Conlogue, G. Garvin, S. Saleem, G. Natale, D. Caramella, and A. Nelson, "Diagnosis by consensus: Interpreting mummified pathological conditions", American Journal of Physical Anthropology, vol. 156, pp. 315-316, 2015.
Nabhan, M. M., S. Brenzinger, J. Carlsson, S. N. Saleem, E. A. Otto, and F. Hildebrandt, "Intrafamilial Variability and Clinical Heterogeneity in Two Siblings with NPHP4 loss of Function Mutations", Journal of Molecular Biomarkers & Diagnosis, vol. 6, issue 217, pp. 1-4, 2015.