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Case report: Expansion of phenotypic and genotypic data in TENM3-related syndrome: Report of two cases

Biallelic TENM3 variants were recently reported to cause non-syndromic microphthalmia with coloboma-9 (MCOPCB9) and microphthalmia and/or coloboma with developmental delay (MCOPS15). To date, only eight syndromic and non-syndromic microphthalmia cases with recessive TENM3 variants have been reported...

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Autores principales: Lu, Fen, Xu, Xin, Zheng, Bixia, Wang, Chunli, Zhou, Wei, Tang, Jian, Zhao, Xiaoke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998998/
https://www.ncbi.nlm.nih.gov/pubmed/36911040
http://dx.doi.org/10.3389/fped.2023.1111771
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author Lu, Fen
Xu, Xin
Zheng, Bixia
Wang, Chunli
Zhou, Wei
Tang, Jian
Zhao, Xiaoke
author_facet Lu, Fen
Xu, Xin
Zheng, Bixia
Wang, Chunli
Zhou, Wei
Tang, Jian
Zhao, Xiaoke
author_sort Lu, Fen
collection PubMed
description Biallelic TENM3 variants were recently reported to cause non-syndromic microphthalmia with coloboma-9 (MCOPCB9) and microphthalmia and/or coloboma with developmental delay (MCOPS15). To date, only eight syndromic and non-syndromic microphthalmia cases with recessive TENM3 variants have been reported. Herein, we report two unrelated new cases with biallelic variants in TENM3, widening the molecular and clinical spectrum. Regarding patient 1, WES revealed compound heterozygous variants in the TENM3 gene: c.3847_3855del; p.Leu1283_Ser1285del and c.3698_3699insA; p.Thr1233Thrfs*20 in the index patient, who was presenting with bilateral microphthalmia, congenital cataract, microcephaly, and global developmental delay. Regarding patient 2, compound missense heterozygous variants in the TENM3 gene were identified: c.941C > T; p.Ala314Val and c.6464T > C; p.Leu2155Pro in the 3-year-old boy, who presented with congenital esotropia, speech delay, and motor developmental delay. The clinical features of these two cases revealed high concordance with the previously reported cases, including microphthalmia and developmental delay. The presence of microcephaly in our patient potentially expands the neurologic phenotype associated with loss of function variants in TENM3, as microcephaly has not previously been described. Furthermore, we present evidence that missense variants in TENM3 are associated with similar, but milder, ocular features.
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spelling pubmed-99989982023-03-11 Case report: Expansion of phenotypic and genotypic data in TENM3-related syndrome: Report of two cases Lu, Fen Xu, Xin Zheng, Bixia Wang, Chunli Zhou, Wei Tang, Jian Zhao, Xiaoke Front Pediatr Pediatrics Biallelic TENM3 variants were recently reported to cause non-syndromic microphthalmia with coloboma-9 (MCOPCB9) and microphthalmia and/or coloboma with developmental delay (MCOPS15). To date, only eight syndromic and non-syndromic microphthalmia cases with recessive TENM3 variants have been reported. Herein, we report two unrelated new cases with biallelic variants in TENM3, widening the molecular and clinical spectrum. Regarding patient 1, WES revealed compound heterozygous variants in the TENM3 gene: c.3847_3855del; p.Leu1283_Ser1285del and c.3698_3699insA; p.Thr1233Thrfs*20 in the index patient, who was presenting with bilateral microphthalmia, congenital cataract, microcephaly, and global developmental delay. Regarding patient 2, compound missense heterozygous variants in the TENM3 gene were identified: c.941C > T; p.Ala314Val and c.6464T > C; p.Leu2155Pro in the 3-year-old boy, who presented with congenital esotropia, speech delay, and motor developmental delay. The clinical features of these two cases revealed high concordance with the previously reported cases, including microphthalmia and developmental delay. The presence of microcephaly in our patient potentially expands the neurologic phenotype associated with loss of function variants in TENM3, as microcephaly has not previously been described. Furthermore, we present evidence that missense variants in TENM3 are associated with similar, but milder, ocular features. Frontiers Media S.A. 2023-02-24 /pmc/articles/PMC9998998/ /pubmed/36911040 http://dx.doi.org/10.3389/fped.2023.1111771 Text en © 2023 Lu, Xu, Zheng, Wang, Zhou, Tang and Zhao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Lu, Fen
Xu, Xin
Zheng, Bixia
Wang, Chunli
Zhou, Wei
Tang, Jian
Zhao, Xiaoke
Case report: Expansion of phenotypic and genotypic data in TENM3-related syndrome: Report of two cases
title Case report: Expansion of phenotypic and genotypic data in TENM3-related syndrome: Report of two cases
title_full Case report: Expansion of phenotypic and genotypic data in TENM3-related syndrome: Report of two cases
title_fullStr Case report: Expansion of phenotypic and genotypic data in TENM3-related syndrome: Report of two cases
title_full_unstemmed Case report: Expansion of phenotypic and genotypic data in TENM3-related syndrome: Report of two cases
title_short Case report: Expansion of phenotypic and genotypic data in TENM3-related syndrome: Report of two cases
title_sort case report: expansion of phenotypic and genotypic data in tenm3-related syndrome: report of two cases
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998998/
https://www.ncbi.nlm.nih.gov/pubmed/36911040
http://dx.doi.org/10.3389/fped.2023.1111771
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