biostudies-literatureHijazi HNEI NIH HHSNHGRI NIH HHSNINDS NIH HHSNIGMS NIH HHS2270-2282https://www.ebi.ac.uk/biostudies/studies/S-EPMC9748253biostudies-literatureUnknown109(12)An Xq22.2 region upstream of PLP1 has been proposed to underly a neurological disease trait when deleted in 46,XX females. Deletion mapping revealed that heterozygous deletions encompassing the smallest region of overlap (SRO) spanning six Xq22.2 genes (BEX3, RAB40A, TCEAL4, TCEAL3, TCEAL1, and MORF4L2) associate with an early-onset neurological disease trait (EONDT) consisting of hypotonia, intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. None of the genes within the SRO have been associated with monogenic disease in OMIM. Through local and international collaborations facilitated by GeneMatcher and Matchmaker Exchange, we have identified and herein report seven de novo variants involving TCEAL1 in seven unrelated families: three hemizygous truncatinAmerican journal of human geneticsTCEAL1 loss-of-function results in an X-linked dominant neurodevelopmental syndrome and drives the neurological disease trait in Xq22.2 deletions.PMC9748253UM1 HG006542R01 GM106373R35 NS105078U01 HG011758R01 NS058529K08 HG008986R01 EY015518R01 EY025718Tabet ACKepczynski LBi WLyulcheva ERosenfeld JASemina EVMuriello MPosey JEHunter JVGibbs RARydzanicz MMarafi DReis LMCarvalho CMBBonneau DRouleau GAGreenhalgh LHijazi HLupski JRHobson GMSyverson EEstiar MAColin ELachmeijer AMABonner DRuaud LCoban-Akdemir ZPehlivan DLevy JGan-Or ZPolatynska KLi YFatih JMTessarech Mvan Jaarsveld RHGuichet ABernstein JAPloski RfalseTCEAL1 loss-of-function results in an X-linked dominant neurodevelopmental syndrome and drives the neurological disease trait in Xq22.2 deletions.An Xq22.2 region upstream of PLP1 has been proposed to underly a neurological disease trait when deleted in 46,XX females. Deletion mapping revealed that heterozygous deletions encompassing the smallest region of overlap (SRO) spanning six Xq22.2 genes (BEX3, RAB40A, TCEAL4, TCEAL3, TCEAL1, and MORF4L2) associate with an early-onset neurological disease trait (EONDT) consisting of hypotonia, intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. None of the genes within the SRO have been associated with monogenic disease in OMIM. Through local and international collaborations facilitated by GeneMatcher and Matchmaker Exchange, we have identified and herein report seven de novo variants involving TCEAL1 in seven unrelated families: three hemizygous truncatin2022-01-01T00:00:00Z2022 Dec2026-05-27T21:02:18.599Z2024-12-04T13:32:40.321ZS-EPMC97482533636832710.1016/j.ajhg.2022.10.007