Journal article

TM4SF20 Ancestral Deletion and Susceptibility to a Pediatric Disorder of Early Language Delay and Cerebral White Matter Hyperintensities

Wojciech Wiszniewski, Jill V Hunter, Neil A Hanchard, Jason R Willer, Chad Shaw, Qi Tian, Anna Illner, Xueqing Wang, Sau W Cheung, Ankita Patel, Ian M Campbell, Violet Gelowani, Patricia Hixson, Audrey R Ester, Mahshid S Azamian, Lorraine Potocki, Gladys Zapata, Patricia P Hernandez, Melissa B Ramocki, Regie LP Santos-Cortez Show all



White matter hyperintensities (WMHs) of the brain are important markers of aging and small-vessel disease. WMHs are rare in healthy children and, when observed, often occur with comorbid neuroinflammatory or vasculitic processes. Here, we describe a complex 4 kb deletion in 2q36.3 that segregates with early childhood communication disorders and WMH in 15 unrelated families predominantly from Southeast Asia. The premature brain aging phenotype with punctate and multifocal WMHs was observed in ~70% of young carrier parents who underwent brain MRI. The complex deletion removes the penultimate exon 3 of TM4SF20, a gene encoding a transmembrane protein of unknown function. Minigene analysis showe..

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University of Melbourne Researchers


Awarded by National Institutes of Health

Awarded by NINDS

Awarded by NHGRI

Awarded by NIMH

Awarded by Simons Foundation (SFARI)

Awarded by Molecular Medicine Scholars Program at BCM

Awarded by NIH/NINDS

Awarded by NIH Intellectual and the Developmental Disabilities Research Grant

Funding Acknowledgements

We are indebted to the families who participated in this research study. Support for this work was provided by the Doris Duke Charitable Foundation (DDCF) and Gillson Longenbaugh Foundation to S.R.L., National Institutes of Health (RO1-HL091771) to J.W.B. and S.R.L., NINDS (RO1-NS058529-03) and NHGRI (5U54HG006542) to J.R.L.; and NIMH (P50-MH094268) and a grant from the Simons Foundation (SFARI # 239983) to N.K. W.W. is supported by a Career Development Award K23NS078056 grant from the NINDS and Molecular Medicine Scholars Program at BCM (HL-66991). M.B.R. is grateful for the support of grant 5K08NS062711 from the NIH/NINDS. M.M.-S. was supported by the McKnight Endowment for Science, Dana Foundation, and the NIH Intellectual and the Developmental Disabilities Research Grant (P30HD024064). S.A.B. is partially funded by a Children's Miracle Network endowed chair in pediatric genetics. N.K. is a Distinguished Jean and George W. Brumley Professor. We thank Emily Hall and Jillian Pearring for technical support. The Department of Molecular and Human Genetics at Baylor College of Medicine offers extensive genetic laboratory testing, including chromosomal microarray analysis, and derives revenue from this activity. J.A.R. is an employee of Signature Genomic Laboratories, a subsidiary of PerkinElmer, Inc.