Browsing by Author "Hashem, Mais"

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    Clinical, neuroimaging, and molecular spectrum of TECPR2‐associated hereditary sensory and autonomic neuropathy with intellectual disability
    (2021) Neuser, Sonja; Brechmann, Barbara; Heimer, Gali; Brösse, Ines; Schubert, Susanna; O'Grady, Lauren; Zech, Michael; Srivastava, Siddharth; Sweetser, David A.; Dincer, Yasemin; Mall, Volker; Winkelmann, Juliane; Behrends, Christian; Darras, Basil T.; Graham, Robert J.; Jayakar, Parul; Byrne, Barry; Bar‐Aluma, Bat El; Haberman, Yael; Szeinberg, Amir; Aldhalaan, Hesham M.; Hashem, Mais; Tenaiji, Amal Al; Ismayl, Omar; Al Nuaimi, Asma E.; Maher, Karima; Ibrahim, Shahnaz; Khan, Fatima; Houlden, Henry; Ramakumaran, Vijayalakshmi S.; Pagnamenta, Alistair T.; Posey, Jennifer E.; Lupski, James R.; Tan, Wen‐Hann; ElGhazali, Gehad; Herman, Isabella; Muñoz, Tatiana; Repetto, Gabriela; Seitz, Angelika; Krumbiegel, Mandy; Poli, Cecilia; Kini, Usha; Efthymiou, Stephanie; Meiler, Jens; Maroofian, Reza; Alkuraya, Fowzan S.; Jamra, Rami Abou; Popp, Bernt; Ben‐Zeev, Bruria; Ebrahimi‐Fakhari, Darius
    Bi‐allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus. Through international collaboration, we identified 17 individuals from 15 families with bi‐allelic TECPR2‐variants. We systemically reviewed clinical and molecular data from this cohort and 11 cases previously reported. Phenotypes were standardized using Human Phenotype Ontology terms. A cross‐ sectional analysis revealed global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea as core manifestations. A review of brain magnetic resonance imaging scans demonstrated a thin corpus callosum in 52%. We evaluated 17 distinct variants. Missense variants in TECPR2 are predominantly located in the N‐ and C‐terminal regions containing β‐propeller repeats. Despite constituting nearly half of disease‐associated TECPR2 variants, classifying missense variants as (likely) pathogenic according to ACMG criteria remains challenging. We estimate a pathogenic variant carrier frequency of 1/1221 in the general and 1/155 in the Jewish Ashkenazi populations. Based on clinical, neuroimaging, and genetic data, we provide recommendations for variant reporting, clinical assessment, and surveillance/ treatment of individuals with TECPR2‐associated disorder. This sets the stage for future prospective natural history studies.
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    Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes
    (BMJ Publishing Group, 2012) Shamseldin, Hanan E; Alshammari, Muneera; Al-Sheddi, Tarfa; Salih, Mustafa A; Alkhalidi, Hisham; Kentab, Amal; Repetto, Gabriela; Hashem, Mais; Alkuraya, Fowzan S
    OBJECTIVE: To investigate the utility of autozygome analysis and exome sequencing in a cohort of patients with suspected or confirmed mitochondrial encephalomyopathy. METHODS: Autozygome was used to highlight candidate genes for direct sequencing in 10 probands, all born to consanguineous parents. Autozygome was also used to filter the variants from exome sequencing of four probands. RESULTS: In addition to revealing mutations in known mitochondrial genes, the analysis revealed the identification of two novel candidate disease genes: MFF and FARS2, encoding the mitochondrial fission factor and phenylalanyl-tRNA synthetase, respectively. INTERPRETATION: These findings expand the repertoire of genes that are mutated in patients with mitochondrial disorders and highlight the value of integrating genomic approaches in the evaluation of these patients.

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