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Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly

We describe a sporadic case of a pure, tandem, interstitial chromosome 4q duplication, arr[hg19] 4q28.1q32.3 (127,008,069-165,250,477) x3 in a boy born at 36 weeks of gestation. He presented with microcephaly (head circumference <1(st) percentile), short stature (height <2(nd) percentile) and...

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Autores principales: Umlai, Umm-Kulthum Ismail, Haris, Basma, Hussain, Khalid, Jithesh, Puthen Veettil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851600/
https://www.ncbi.nlm.nih.gov/pubmed/35185781
http://dx.doi.org/10.3389/fendo.2021.783235
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author Umlai, Umm-Kulthum Ismail
Haris, Basma
Hussain, Khalid
Jithesh, Puthen Veettil
author_facet Umlai, Umm-Kulthum Ismail
Haris, Basma
Hussain, Khalid
Jithesh, Puthen Veettil
author_sort Umlai, Umm-Kulthum Ismail
collection PubMed
description We describe a sporadic case of a pure, tandem, interstitial chromosome 4q duplication, arr[hg19] 4q28.1q32.3 (127,008,069-165,250,477) x3 in a boy born at 36 weeks of gestation. He presented with microcephaly (head circumference <1(st) percentile), short stature (height <2(nd) percentile) and poor weight gain (weight <3(rd) percentile). Hypospadias and horseshoe shaped kidneys were also revealed following a urinary tract ultrasound. Biochemical analysis revealed normal growth hormone and thyroid hormone levels. While gross and fine motor skill development was in line with his age, speech delay was observed. This patient adds to a group of more than 30 cases of pure 4q tandem duplication with common and differing phenotypic presentations. Using a retrospective analysis of previous case studies alongside the current case and bioinformatics analysis of the duplicated region, we deduced the most likely dosage sensitive genes for some of the major phenotypes in the patient. The positive predictive value (PPV) was calculated for each gene and phenotype and was derived by comparing the previously reported patients who have gene duplications and an associated phenotype versus those who had the gene duplications but were unaffected. Thus, the growth retardation phenotype may be associated with NAA15 duplication, speech delay with GRIA2 and microcephaly with PLK4 duplication. Functional studies will help in confirming the observations and elucidating the mechanisms. However, our study highlights the importance of analysing case reports with pure duplications in defining phenotype-gene relationships and in improving our knowledge of the function of precise chromosomal regions.
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spelling pubmed-88516002022-02-18 Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly Umlai, Umm-Kulthum Ismail Haris, Basma Hussain, Khalid Jithesh, Puthen Veettil Front Endocrinol (Lausanne) Endocrinology We describe a sporadic case of a pure, tandem, interstitial chromosome 4q duplication, arr[hg19] 4q28.1q32.3 (127,008,069-165,250,477) x3 in a boy born at 36 weeks of gestation. He presented with microcephaly (head circumference <1(st) percentile), short stature (height <2(nd) percentile) and poor weight gain (weight <3(rd) percentile). Hypospadias and horseshoe shaped kidneys were also revealed following a urinary tract ultrasound. Biochemical analysis revealed normal growth hormone and thyroid hormone levels. While gross and fine motor skill development was in line with his age, speech delay was observed. This patient adds to a group of more than 30 cases of pure 4q tandem duplication with common and differing phenotypic presentations. Using a retrospective analysis of previous case studies alongside the current case and bioinformatics analysis of the duplicated region, we deduced the most likely dosage sensitive genes for some of the major phenotypes in the patient. The positive predictive value (PPV) was calculated for each gene and phenotype and was derived by comparing the previously reported patients who have gene duplications and an associated phenotype versus those who had the gene duplications but were unaffected. Thus, the growth retardation phenotype may be associated with NAA15 duplication, speech delay with GRIA2 and microcephaly with PLK4 duplication. Functional studies will help in confirming the observations and elucidating the mechanisms. However, our study highlights the importance of analysing case reports with pure duplications in defining phenotype-gene relationships and in improving our knowledge of the function of precise chromosomal regions. Frontiers Media S.A. 2022-02-03 /pmc/articles/PMC8851600/ /pubmed/35185781 http://dx.doi.org/10.3389/fendo.2021.783235 Text en Copyright © 2022 Umlai, Haris, Hussain and Jithesh 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). 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 Endocrinology
Umlai, Umm-Kulthum Ismail
Haris, Basma
Hussain, Khalid
Jithesh, Puthen Veettil
Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly
title Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly
title_full Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly
title_fullStr Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly
title_full_unstemmed Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly
title_short Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly
title_sort case report: phenotype-gene correlation in a case of novel tandem 4q microduplication with short stature, speech delay and microcephaly
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851600/
https://www.ncbi.nlm.nih.gov/pubmed/35185781
http://dx.doi.org/10.3389/fendo.2021.783235
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