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Identification of Novel ROR2 Gene Mutations in Indian Children with Robinow Syndrome
Objective: Robinow syndrome (RS) is an extremely rare genetic disorder characterized by short-limbed dwarfism, defects in vertebral segmentation and abnormalities in the head, face and external genitalia. Mutations in the ROR2 gene cause autosomal recessive RS (RRS) whereas mutations in WNT5A are...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Galenos Publishing
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141580/ https://www.ncbi.nlm.nih.gov/pubmed/24932600 http://dx.doi.org/10.4274/jcrpe.1233 |
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author | Tamhankar, Parag M Vasudevan, Lakshmi Kondurkar, Shweta K, Yashaswini Agarwalla, Sunil Kumar Nair, Mohandas TV, Ramkumar Chaubal, Nitin Chennuri, Vasundhara Sridhar |
author_facet | Tamhankar, Parag M Vasudevan, Lakshmi Kondurkar, Shweta K, Yashaswini Agarwalla, Sunil Kumar Nair, Mohandas TV, Ramkumar Chaubal, Nitin Chennuri, Vasundhara Sridhar |
author_sort | Tamhankar, Parag M |
collection | PubMed |
description | Objective: Robinow syndrome (RS) is an extremely rare genetic disorder characterized by short-limbed dwarfism, defects in vertebral segmentation and abnormalities in the head, face and external genitalia. Mutations in the ROR2 gene cause autosomal recessive RS (RRS) whereas mutations in WNT5A are responsible for the autosomal dominant (AD) form of RS. In AD Robinow patients, oral manifestations are more prominent, while hemivertebrae and scoliosis rarely occur and facial abnormalities tend to be milder. Methods: Three unrelated patients from different parts of India were studied. These patients were diagnosed as RRS due to presence of characteristic fetal facies, mesomelia, short stature, micropenis, hemivertebrae and rib abnormalities. One of the patients had fetal facies and micropenis but unusually mild skeletal features. This patient’s mother had mild affection in the form of short stature and prominent eyes. Testosterone response to human chorionic gonadotropin was investigated in two patients and were normal. The exons and exon-intron boundaries of the ROR2 gene were sequenced for all probands. Bioinformatics analysis was done for putative variants using SIFT, PolyPhen2 and Mutation Taster. Results: Patients 1, 2 and 3 were homozygous for c.G545A or p.C182Y in exon 5, c.227G>A or p.G76D in exon 3 and c.668G>A or p.C223Y in exon 6 respectively. Prenatal diagnosis could be performed in an ongoing pregnancy in one family and the fetus was confirmed to be unaffected. Conclusion: ROR2 mutations were documented for the first time in the Indian population. Knowledge of the molecular basis of the disorder served to provide accurate counseling and prenatal diagnosis to the families. |
format | Online Article Text |
id | pubmed-4141580 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Galenos Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-41415802014-08-22 Identification of Novel ROR2 Gene Mutations in Indian Children with Robinow Syndrome Tamhankar, Parag M Vasudevan, Lakshmi Kondurkar, Shweta K, Yashaswini Agarwalla, Sunil Kumar Nair, Mohandas TV, Ramkumar Chaubal, Nitin Chennuri, Vasundhara Sridhar J Clin Res Pediatr Endocrinol Original Article Objective: Robinow syndrome (RS) is an extremely rare genetic disorder characterized by short-limbed dwarfism, defects in vertebral segmentation and abnormalities in the head, face and external genitalia. Mutations in the ROR2 gene cause autosomal recessive RS (RRS) whereas mutations in WNT5A are responsible for the autosomal dominant (AD) form of RS. In AD Robinow patients, oral manifestations are more prominent, while hemivertebrae and scoliosis rarely occur and facial abnormalities tend to be milder. Methods: Three unrelated patients from different parts of India were studied. These patients were diagnosed as RRS due to presence of characteristic fetal facies, mesomelia, short stature, micropenis, hemivertebrae and rib abnormalities. One of the patients had fetal facies and micropenis but unusually mild skeletal features. This patient’s mother had mild affection in the form of short stature and prominent eyes. Testosterone response to human chorionic gonadotropin was investigated in two patients and were normal. The exons and exon-intron boundaries of the ROR2 gene were sequenced for all probands. Bioinformatics analysis was done for putative variants using SIFT, PolyPhen2 and Mutation Taster. Results: Patients 1, 2 and 3 were homozygous for c.G545A or p.C182Y in exon 5, c.227G>A or p.G76D in exon 3 and c.668G>A or p.C223Y in exon 6 respectively. Prenatal diagnosis could be performed in an ongoing pregnancy in one family and the fetus was confirmed to be unaffected. Conclusion: ROR2 mutations were documented for the first time in the Indian population. Knowledge of the molecular basis of the disorder served to provide accurate counseling and prenatal diagnosis to the families. Galenos Publishing 2014-06 2014-06-05 /pmc/articles/PMC4141580/ /pubmed/24932600 http://dx.doi.org/10.4274/jcrpe.1233 Text en © Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Tamhankar, Parag M Vasudevan, Lakshmi Kondurkar, Shweta K, Yashaswini Agarwalla, Sunil Kumar Nair, Mohandas TV, Ramkumar Chaubal, Nitin Chennuri, Vasundhara Sridhar Identification of Novel ROR2 Gene Mutations in Indian Children with Robinow Syndrome |
title | Identification of Novel ROR2 Gene Mutations in Indian Children with Robinow Syndrome |
title_full | Identification of Novel ROR2 Gene Mutations in Indian Children with Robinow Syndrome |
title_fullStr | Identification of Novel ROR2 Gene Mutations in Indian Children with Robinow Syndrome |
title_full_unstemmed | Identification of Novel ROR2 Gene Mutations in Indian Children with Robinow Syndrome |
title_short | Identification of Novel ROR2 Gene Mutations in Indian Children with Robinow Syndrome |
title_sort | identification of novel ror2 gene mutations in indian children with robinow syndrome |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141580/ https://www.ncbi.nlm.nih.gov/pubmed/24932600 http://dx.doi.org/10.4274/jcrpe.1233 |
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