@article {941, title = {MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia.}, journal = {Ann Neurol}, volume = {89}, year = {2021}, month = {2021 04}, pages = {828-833}, abstract = {

The Mediator multiprotein complex functions as a regulator of RNA polymerase II-catalyzed gene transcription. In this study, exome sequencing detected biallelic putative disease-causing variants in MED27, encoding Mediator complex subunit 27, in 16 patients from 11 families with a novel neurodevelopmental syndrome. Patient phenotypes are highly homogeneous, including global developmental delay, intellectual disability, axial hypotonia with distal spasticity, dystonic movements, and cerebellar hypoplasia. Seizures and cataracts were noted in severely affected individuals. Identification of multiple patients with biallelic MED27 variants supports the critical role of MED27 in normal human neural development, particularly for the cerebellum. ANN NEUROL 2021;89:828-833.

}, keywords = {Adolescent, Adult, Amino Acid Sequence, Cataract, Cerebellum, Child, Child, Preschool, Developmental Disabilities, Dystonia, Epilepsy, Genetic Variation, Humans, Infant, Mediator Complex, Nervous System Malformations, Phenotype, Whole Exome Sequencing}, issn = {1531-8249}, doi = {10.1002/ana.26019}, author = {Meng, Linyan and Isohanni, Pirjo and Shao, Yunru and GrAHm, Brett H and Hickey, Scott E and Brooks, Stephanie and Suomalainen, Anu and Joset, Pascal and Steindl, Katharina and Rauch, Anita and Hackenberg, Annette and High, Frances A and Armstrong-Javors, Amy and Mencacci, Niccol{\`o} E and Gonz{\`a}lez-Latapi, Paulina and Kamel, Walaa A and Al-Hashel, Jasem Y and Bustos, Bernab{\'e} I and Hernandez, Alejandro V and Krainc, Dimitri and Lubbe, Steven J and Van Esch, Hilde and De Luca, Chiara and Ballon, Katleen and Ravelli, Claudia and Burglen, Lydie and Qebibo, Leila and Calame, Daniel G and Mitani, Tadahiro and Marafi, Dana and Pehlivan, Davut and Saadi, Nebal W and Sahin, Yavuz and Maroofian, Reza and Efthymiou, Stephanie and Houlden, Henry and Maqbool, Shazia and Rahman, Fatima and Gu, Shen and Posey, Jennifer E and Lupski, James R and Hunter, Jill V and Wangler, Michael F and Carroll, Christopher J and Yang, Yaping} } @article {886, title = {Community-based recruitment and exome sequencing indicates high diagnostic yield in adults with intellectual disability.}, journal = {Mol Genet Genomic Med}, volume = {8}, year = {2020}, month = {2020 10}, pages = {e1439}, abstract = {

BACKGROUND: Establishing a genetic diagnosis for individuals with intellectual disability (ID) benefits patients and their families as it may inform the prognosis, lead to appropriate therapy, and facilitate access to medical and supportive services. Exome sequencing has been successfully applied in a diagnostic setting, but most clinical exome referrals are pediatric patients, with many adults with ID lacking a comprehensive genetic evaluation.

METHODS: Our unique recruitment strategy involved partnering with service and education providers for individuals with ID. We performed exome sequencing and analysis, and clinical variant interpretation for each recruited family.

RESULTS: All five families enrolled in the study opted-in for the return of genetic results. In three out of five families exome sequencing analysis identified pathogenic or likely pathogenic variants in KANSL1, TUSC3, and MED13L genes. Families discussed the results and any potential medical follow-up in an appointment with a board certified clinical geneticist.

CONCLUSION: Our study suggests high yield of exome sequencing as a diagnostic tool in adult patients with ID who have not undergone comprehensive sequencing-based genetic testing. Research studies including an option of return of results through a genetic clinic could help minimize the disparity in exome diagnostic testing between pediatric and adult patients with ID.

}, keywords = {Adult, Female, Genetic Testing, Humans, Independent Living, Intellectual Disability, Male, Mediator Complex, Membrane Proteins, Nuclear Proteins, Patient Selection, Sensitivity and Specificity, Tumor Suppressor Proteins, Whole Exome Sequencing}, issn = {2324-9269}, doi = {10.1002/mgg3.1439}, author = {Sabo, Aniko and Murdock, David and Dugan, Shannon and Meng, Qingchang and Gingras, Marie-Claude and Hu, Jianhong and Muzny, Donna and Gibbs, Richard} }