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A Novel Homozygous Frameshift Variant in XYLT2 Causes Spondyloocular Syndrome in a Consanguineous Pakistani Family
We report on three new patients with spondyloocular syndrome (SOS) in a consanguineous Pakistani family. All three patients present progressive generalized osteoporosis, short stature, recurrent fractures, hearing loss and visual impairments. WES revealed a novel homozygous frameshift variant in exo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411848/ https://www.ncbi.nlm.nih.gov/pubmed/30891060 http://dx.doi.org/10.3389/fgene.2019.00144 |
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author | Kausar, Mehran Chew, Elaine Guo Yan Ullah, Hazrat Anees, Mariam Khor, Chiea Chuen Foo, Jia Nee Makitie, Outi Siddiqi, Saima |
author_facet | Kausar, Mehran Chew, Elaine Guo Yan Ullah, Hazrat Anees, Mariam Khor, Chiea Chuen Foo, Jia Nee Makitie, Outi Siddiqi, Saima |
author_sort | Kausar, Mehran |
collection | PubMed |
description | We report on three new patients with spondyloocular syndrome (SOS) in a consanguineous Pakistani family. All three patients present progressive generalized osteoporosis, short stature, recurrent fractures, hearing loss and visual impairments. WES revealed a novel homozygous frameshift variant in exon 11 of XYLT2 (NG 012175.1, NP_071450.2) resulting in loss of evolutionary conserved amino acid sequences (840 – 865/865) at C-terminus p.R840fs(∗)115. Sanger Sequencing confirmed the presence of the novel homozygous mutation in all three patients while the parents were heterozygous carriers of the mutation, in accordance with an autosomal recessive inheritance pattern. Only nine variants worldwide have previously been reported in XYLT2 in patients with SOS phenotype. These three patients with novel homozygous variant extend the genotypic and phenotypic spectrum of SOS. |
format | Online Article Text |
id | pubmed-6411848 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64118482019-03-19 A Novel Homozygous Frameshift Variant in XYLT2 Causes Spondyloocular Syndrome in a Consanguineous Pakistani Family Kausar, Mehran Chew, Elaine Guo Yan Ullah, Hazrat Anees, Mariam Khor, Chiea Chuen Foo, Jia Nee Makitie, Outi Siddiqi, Saima Front Genet Genetics We report on three new patients with spondyloocular syndrome (SOS) in a consanguineous Pakistani family. All three patients present progressive generalized osteoporosis, short stature, recurrent fractures, hearing loss and visual impairments. WES revealed a novel homozygous frameshift variant in exon 11 of XYLT2 (NG 012175.1, NP_071450.2) resulting in loss of evolutionary conserved amino acid sequences (840 – 865/865) at C-terminus p.R840fs(∗)115. Sanger Sequencing confirmed the presence of the novel homozygous mutation in all three patients while the parents were heterozygous carriers of the mutation, in accordance with an autosomal recessive inheritance pattern. Only nine variants worldwide have previously been reported in XYLT2 in patients with SOS phenotype. These three patients with novel homozygous variant extend the genotypic and phenotypic spectrum of SOS. Frontiers Media S.A. 2019-03-05 /pmc/articles/PMC6411848/ /pubmed/30891060 http://dx.doi.org/10.3389/fgene.2019.00144 Text en Copyright © 2019 Kausar, Chew, Ullah, Anees, Khor, Foo, Makitie and Siddiqi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). 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 | Genetics Kausar, Mehran Chew, Elaine Guo Yan Ullah, Hazrat Anees, Mariam Khor, Chiea Chuen Foo, Jia Nee Makitie, Outi Siddiqi, Saima A Novel Homozygous Frameshift Variant in XYLT2 Causes Spondyloocular Syndrome in a Consanguineous Pakistani Family |
title | A Novel Homozygous Frameshift Variant in XYLT2 Causes Spondyloocular Syndrome in a Consanguineous Pakistani Family |
title_full | A Novel Homozygous Frameshift Variant in XYLT2 Causes Spondyloocular Syndrome in a Consanguineous Pakistani Family |
title_fullStr | A Novel Homozygous Frameshift Variant in XYLT2 Causes Spondyloocular Syndrome in a Consanguineous Pakistani Family |
title_full_unstemmed | A Novel Homozygous Frameshift Variant in XYLT2 Causes Spondyloocular Syndrome in a Consanguineous Pakistani Family |
title_short | A Novel Homozygous Frameshift Variant in XYLT2 Causes Spondyloocular Syndrome in a Consanguineous Pakistani Family |
title_sort | novel homozygous frameshift variant in xylt2 causes spondyloocular syndrome in a consanguineous pakistani family |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411848/ https://www.ncbi.nlm.nih.gov/pubmed/30891060 http://dx.doi.org/10.3389/fgene.2019.00144 |
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