Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly
<p dir="ltr">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<sup>st</sup> percentile)...
محفوظ في:
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| مؤلفون آخرون: | , , |
| منشور في: |
2022
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إضافة وسم
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| _version_ | 1864513519679963136 |
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| author | Umm-Kulthum Ismail Umlai (12040352) |
| author2 | Basma Haris (12040355) Khalid Hussain (110443) Puthen Veettil Jithesh (12040358) |
| author2_role | author author author |
| author_facet | Umm-Kulthum Ismail Umlai (12040352) Basma Haris (12040355) Khalid Hussain (110443) Puthen Veettil Jithesh (12040358) |
| author_role | author |
| dc.creator.none.fl_str_mv | Umm-Kulthum Ismail Umlai (12040352) Basma Haris (12040355) Khalid Hussain (110443) Puthen Veettil Jithesh (12040358) |
| dc.date.none.fl_str_mv | 2022-02-03T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fendo.2021.783235 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Case_Report_Phenotype-Gene_Correlation_in_a_Case_of_Novel_Tandem_4q_Microduplication_With_Short_Stature_Speech_Delay_and_Microcephaly/25516180 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences chromosomal duplication chromosome 4 balanced translocation rare diseases short stature horseshoe kidneys speech delay microcephaly |
| dc.title.none.fl_str_mv | Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">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<sup>st</sup> percentile), short stature (height <<sup>2nd</sup> percentile) and poor weight gain (weight <3<sup>rd</sup> 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.</p><p dir="ltr"><br></p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Endocrinology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fendo.2021.783235" target="_blank">https://dx.doi.org/10.3389/fendo.2021.783235</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_a62ca569ed845b7e18161ac1c24885d8 |
| identifier_str_mv | 10.3389/fendo.2021.783235 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25516180 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and MicrocephalyUmm-Kulthum Ismail Umlai (12040352)Basma Haris (12040355)Khalid Hussain (110443)Puthen Veettil Jithesh (12040358)Biomedical and clinical sciencesClinical scienceschromosomal duplicationchromosome 4balanced translocationrare diseasesshort staturehorseshoe kidneysspeech delaymicrocephaly<p dir="ltr">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<sup>st</sup> percentile), short stature (height <<sup>2nd</sup> percentile) and poor weight gain (weight <3<sup>rd</sup> 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.</p><p dir="ltr"><br></p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Endocrinology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fendo.2021.783235" target="_blank">https://dx.doi.org/10.3389/fendo.2021.783235</a></p>2022-02-03T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fendo.2021.783235https://figshare.com/articles/journal_contribution/Case_Report_Phenotype-Gene_Correlation_in_a_Case_of_Novel_Tandem_4q_Microduplication_With_Short_Stature_Speech_Delay_and_Microcephaly/25516180CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/255161802022-02-03T03:00:00Z |
| spellingShingle | Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly Umm-Kulthum Ismail Umlai (12040352) Biomedical and clinical sciences Clinical sciences chromosomal duplication chromosome 4 balanced translocation rare diseases short stature horseshoe kidneys speech delay microcephaly |
| status_str | publishedVersion |
| 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 | Biomedical and clinical sciences Clinical sciences chromosomal duplication chromosome 4 balanced translocation rare diseases short stature horseshoe kidneys speech delay microcephaly |