Notch1 down-regulation in lineage-restricted niches of mouse eccrine sweat glands

Wang, Yuzhen; Yao, Bin; Duan, Xianlan; Li, Jianjun; Song, Wei; Jirigala, Enhe; Zhao, Li; Yuan, Xingyu; Kong, Yi; Zhang, Yijie; Fu, Xiaobing; Huang, Sha

doi:10.21203/rs.3.rs-596907/v1

Cited by 1 publication

(1 citation statement)

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“…While TSPEAR expression in nails, sweat and salivary glands has not been studied, Notch signaling is involved in their organogeneses in mice. Downregulation of Notch1 directs sweat gland differentiation, while its upregulation is required for salivary glands’ differentiation and growth and promoting mitosis in the nail matrix [ 73 , 74 , 75 ]. The ten reported patients herein had ED without hypohidrosis, but only one patient showed decreased salivary flow, which has not been reported in TSPEAR -ED cases before.…”

Section: Discussionmentioning

confidence: 99%

Confirmation of a Phenotypic Entity for TSPEAR Variants in Egyptian Ectodermal Dysplasia Patients and Role of Ethnicity

Rabie

Sayed

Amr

et al. 2022

Genes

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Ectodermal dysplasia (ED) are hereditary disorders characterized by the disturbance of the ectodermal development of at least two of four ectodermal tissues: teeth, hair, nails and sweat glands. Clinical classification of ED is challenged by overlapping features, variable expressivity, and low number of patients, hindering full phenotypic spectrum identification. Disease-causing variants in elements of major developmental pathways, e.g., Ectodysplasin/NFκB, Wnt, and Tp63 pathways, have been identified in fewer than half of ED phenotypes. Whole-exome sequencing (WES) was performed for ten Egyptian ED patients presenting with tooth agenesis, normal sweating, scalp hypotrichosis, and sharing characteristic facial features. WES was followed by in silico analysis of the effects of novel detected genetic variants on mRNA and protein structure. The study identified four novel rare pathogenic and likely pathogenic TSPEAR variants, a gene which was recently found to be involved in ectodermal organogenesis. A novel in-frame deletion recurred in eight patients from six unrelated families. Comparing our cohort to previously reported TSPEAR cohorts highlighted the influence of ethnicity on TSPEAR phenotypic affection. Our study expands the clinical and mutational spectrum of the growing TSPEAR associated phenotypes, and pinpoints the influence of WES and in silico tools on identification of rare disease-causing variants.

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Section: Discussionmentioning

confidence: 99%