High yield of monogenic short stature in children from Kurdistan, Iraq: A genetic testing algorithm for consanguineous families

Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique pediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic tes...

Full description

Saved in:
Bibliographic Details
Published in:Genetics in medicine Vol. 27; no. 2; p. 101332
Main Authors: Amaratunga, Shenali Anne, Tayeb, Tara Hussein, Dusatkova, Petra, Elblova, Lenka, Drabova, Jana, Plachy, Lukas, Pruhova, Stepanka, Lebl, Jan
Format: Journal Article
Language:English
Published: United States 01.02.2025
Subjects:
Adolescent
Algorithms
Body Height - genetics
Child
Child, Preschool
Consanguinity
Dwarfism - diagnosis
Dwarfism - epidemiology
Dwarfism - genetics
Exome Sequencing
Female
Genetic Testing - methods
Humans
Iraq - epidemiology
Male
Pedigree
Iraq
Genetic testing algorithm
Short stature
Consanguinity
Short stature genes
Pediatric endocrinology
ISSN:1530-0366, 1530-0366
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Abstract Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique pediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations. Among 280 SS referrals from 2018-2020, 64 children met inclusion criteria (from consanguineous families; height ≤ -2.25 SD), 51 provided informed consent (30 females; 31 syndromic SS) and underwent investigation, primarily via exome sequencing. Prioritized variants were evaluated by the American College of Medical Genetics and Genomics standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS. A genetic cause of SS was elucidated in 31 of 51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR and SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, and SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, and LIG4), cytoskeletal structure (CCDC8, FLNA, and PCNT), transmembrane transport (SLC34A3 and SLC7A7), enzyme coding (CYP27B1, GALNS, and GNPTG), and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and 1 had del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10% to 33% of cases. A tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.
AbstractList Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique paediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations.INTRODUCTIONGenetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique paediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations.Among 280 SS referrals 2018-2020, 64 children met inclusion criteria (from consanguineous families; height ≤-2.25 SD), 51 provided informed consent (30 females; 31 syndromic SS) and underwent investigation, primarily via exome sequencing. Prioritized variants were evaluated by ACMG standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS.METHODSAmong 280 SS referrals 2018-2020, 64 children met inclusion criteria (from consanguineous families; height ≤-2.25 SD), 51 provided informed consent (30 females; 31 syndromic SS) and underwent investigation, primarily via exome sequencing. Prioritized variants were evaluated by ACMG standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS.A genetic cause of SS was elucidated in 31/51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR, SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, LIG4), cytoskeletal structure (CCDC8, FLNA, PCNT), transmembrane transport (SLC34A3, SLC7A7), enzyme coding (CYP27B1, GALNS, GNPTG) and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and one del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10-33% of cases.RESULTSA genetic cause of SS was elucidated in 31/51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR, SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, LIG4), cytoskeletal structure (CCDC8, FLNA, PCNT), transmembrane transport (SLC34A3, SLC7A7), enzyme coding (CYP27B1, GALNS, GNPTG) and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and one del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10-33% of cases.A tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.CONCLUSIONA tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.
Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique pediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations. Among 280 SS referrals from 2018-2020, 64 children met inclusion criteria (from consanguineous families; height ≤ -2.25 SD), 51 provided informed consent (30 females; 31 syndromic SS) and underwent investigation, primarily via exome sequencing. Prioritized variants were evaluated by the American College of Medical Genetics and Genomics standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS. A genetic cause of SS was elucidated in 31 of 51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR and SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, and SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, and LIG4), cytoskeletal structure (CCDC8, FLNA, and PCNT), transmembrane transport (SLC34A3 and SLC7A7), enzyme coding (CYP27B1, GALNS, and GNPTG), and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and 1 had del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10% to 33% of cases. A tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.
Author Pruhova, Stepanka
Plachy, Lukas
Lebl, Jan
Elblova, Lenka
Drabova, Jana
Tayeb, Tara Hussein
Dusatkova, Petra
Amaratunga, Shenali Anne
Author_xml – sequence: 1
  givenname: Shenali Anne
  surname: Amaratunga
  fullname: Amaratunga, Shenali Anne
  organization: Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic
– sequence: 2
  givenname: Tara Hussein
  surname: Tayeb
  fullname: Tayeb, Tara Hussein
  organization: Department of Paediatrics, Sulaimani University, College of Medicine, Sulaimani, Iraq
– sequence: 3
  givenname: Petra
  surname: Dusatkova
  fullname: Dusatkova, Petra
  organization: Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic
– sequence: 4
  givenname: Lenka
  surname: Elblova
  fullname: Elblova, Lenka
  organization: Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic
– sequence: 5
  givenname: Jana
  surname: Drabova
  fullname: Drabova, Jana
  organization: Department of Biology and Medical Genetics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic
– sequence: 6
  givenname: Lukas
  surname: Plachy
  fullname: Plachy, Lukas
  organization: Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic
– sequence: 7
  givenname: Stepanka
  surname: Pruhova
  fullname: Pruhova, Stepanka
  organization: Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic
– sequence: 8
  givenname: Jan
  surname: Lebl
  fullname: Lebl, Jan
  email: jan.lebl@lfmotol.cuni.cz
  organization: Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic. Electronic address: jan.lebl@lfmotol.cuni.cz
BackLink https://www.ncbi.nlm.nih.gov/pubmed/39580647$$D View this record in MEDLINE/PubMed
BookMark eNpNULtOwzAUtRCIPuADWJBHBlL8iPNgqyqgFZVYYI6c5DpxFdutnQyd-HUCFInpnqPz0NGdoXPrLCB0Q8mCEpo87BaNNgtGWPzNOWdnaEoFJxHhSXL-D0_QLIQdITTljFyiCc9FRpI4naLPtW5afNTQ1dgpbJx1DVhd4dA63-PQy37wgLXFVau72oPFyjuDXwdf61G193jj5eERL_GYg35M9hB6bRssu8Z53bcGK-dx5WyQthm0BTcErKTRnYZwhS6U7AJcn-4cfTw_va_W0fbtZbNabqOKE9FHUoAQjMpKAcuBi5gqltZUckFVpngCMFJRyTyrszKFUpCYlELWKVQso1nO5ujut3fv3WEYFxZGhwq6Tv7sKTjlLCG54PFovT1Zh9JAXey9NtIfi7-nsS_I8nMr
ContentType Journal Article
Copyright Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
Copyright © 2024. Published by Elsevier Inc.
Copyright_xml – notice: Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
– notice: Copyright © 2024. Published by Elsevier Inc.
DBID CGR
CUY
CVF
ECM
EIF
NPM
7X8
DOI 10.1016/j.gim.2024.101332
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic
MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod no_fulltext_linktorsrc
Discipline Medicine
Biology
EISSN 1530-0366
ExternalDocumentID 39580647
Genre Journal Article
GeographicLocations Iraq
GeographicLocations_xml – name: Iraq
GroupedDBID ---
.-D
..I
.GJ
08G
39C
4Q1
4Q2
4Q3
53G
5GY
5RE
5VS
70F
7X7
88E
8FI
8FJ
AAFWJ
AAKAS
AALRI
AAXUO
AAYEP
AAYWO
ABAWZ
ABJNI
ABLJU
ABUWG
ACGFO
ACGFS
ACKTT
ACRQY
ACVFH
ADBBV
ADBIZ
ADCNI
ADVLN
ADZCM
AE3
AEJRE
AENEX
AEUPX
AEXYK
AFETI
AFJKZ
AFKRA
AFPUW
AFSHS
AFTRI
AGAYW
AGCQF
AHMBA
AHSBF
AHVBC
AIGII
AILAN
AITUG
AIZYK
AJRNO
AKBMS
AKRWK
AKYEP
ALFFA
ALIPV
ALMA_UNASSIGNED_HOLDINGS
AMRAJ
APXCP
AXYYD
BENPR
BKKNO
BPHCQ
BS7
BVXVI
CCPQU
CGR
CS3
CUY
CVF
DNIVK
DU5
EBS
ECM
EE.
EFKBS
EIF
EIOEI
EJD
EX3
F5P
FDB
FDQFY
FERAY
FIZPM
FSGXE
FYUFA
H0~
HMCUK
JF9
JG8
JK3
JSO
K-O
KD2
M1P
M41
N9A
NPM
NQJWS
N~M
OAG
OAH
ODA
OK1
OLG
OVD
OWU
OWV
OWW
OWX
OWY
OWZ
P-K
P2P
PHGZM
PHGZT
PJZUB
PPXIY
PQQKQ
PROAC
PSQYO
R58
RNT
RNTTT
ROL
S4R
SNYQT
SOHCF
SOJ
SRMVM
SWTZT
T8P
TAOOD
TBHMF
TDRGL
TEORI
TSG
UKHRP
VVN
W3M
WOQ
WOW
XXN
XYM
YFH
ZFV
7X8
EBLON
ID FETCH-LOGICAL-c305t-a5e5521acfe29e3541f27d1a351f8f36ee27d5ca98d8b7eb5040b5ad7ec281892
IEDL.DBID 7X8
ISICitedReferencesCount 0
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001414276100001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 1530-0366
IngestDate Sun Sep 28 04:44:50 EDT 2025
Mon Jul 21 05:51:32 EDT 2025
IsPeerReviewed true
IsScholarly true
Issue 2
Keywords Genetic testing algorithm
Short stature
Consanguinity
Short stature genes
Pediatric endocrinology
Language English
License Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c305t-a5e5521acfe29e3541f27d1a351f8f36ee27d5ca98d8b7eb5040b5ad7ec281892
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
PMID 39580647
PQID 3132609534
PQPubID 23479
ParticipantIDs proquest_miscellaneous_3132609534
pubmed_primary_39580647
PublicationCentury 2000
PublicationDate 2025-02-01
PublicationDateYYYYMMDD 2025-02-01
PublicationDate_xml – month: 02
  year: 2025
  text: 2025-02-01
  day: 01
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle Genetics in medicine
PublicationTitleAlternate Genet Med
PublicationYear 2025
SSID ssj0017320
Score 2.4352849
Snippet Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain...
SourceID proquest
pubmed
SourceType Aggregation Database
Index Database
StartPage 101332
SubjectTerms Adolescent
Algorithms
Body Height - genetics
Child
Child, Preschool
Consanguinity
Dwarfism - diagnosis
Dwarfism - epidemiology
Dwarfism - genetics
Exome Sequencing
Female
Genetic Testing - methods
Humans
Iraq - epidemiology
Male
Pedigree
Title High yield of monogenic short stature in children from Kurdistan, Iraq: A genetic testing algorithm for consanguineous families
URI https://www.ncbi.nlm.nih.gov/pubmed/39580647
https://www.proquest.com/docview/3132609534
Volume 27
WOSCitedRecordID wos001414276100001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings 1
isFullTextHit
isPrint
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1bS8MwFA7e8cXLvN84go8G1zZtWl9ExKHIxh4U9jbSNNkG2s61E3zyr3tO1uGTIPhSCCE0JF9OTs7tY-wilbbZtMbnFtHDRRQrHqsg5ZFG9SKSBnuVI5uQnU7c6yXd2uBW1mGVc5noBHVWaLKRX1GJQVccTdyM3zmxRpF3tabQWGTL2J8QqmXvx4sgA1eWEQ91k6OkjuZeTRffNRhRIrovqB0Q-8hvGqa7aVqb_53jFtuodUy4nYFimy2YvMFWZ6yTnw221q796Tvsi8I84JOi2KCwgOMLBNRIQzlEtRwo22g6MTDKYZ70DZSPAk9TxBXplZfwOFHv16AAx1E-JFRUtiMfgHod4NSq4RugWgz46i7JMop_LaYlOLMKvtF32Uvr_vnugdeUDFyjYKi4Ck2IF77SuL2JCULhWV9mngpCz8Y2iIzBZqhVEmdxKk0aooxIQ5VJo6nsVOLvsaW8yM0Bg0DGwsgoMzLBGzJFVVAaTyirhZdGIhOH7Hy-yH2EPPkxlJtj_2eZD9n-bKf641ltjn6QhDHlzx79YfQxW_eJzdfFYJ-wZYsH3pyyFf1RjcrJmcMSfjvd9jef6tTj
linkProvider ProQuest
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=High+yield+of+monogenic+short+stature+in+children+from+Kurdistan%2C+Iraq%3A+a+genetic+testing+algorithm+for+consanguineous+families&rft.jtitle=Genetics+in+medicine&rft.au=Amaratunga%2C+Shenali+Anne&rft.au=Hussein+Tayeb%2C+Tara&rft.au=Dusatkova%2C+Petra&rft.au=Elblova%2C+Lenka&rft.date=2025-02-01&rft.issn=1530-0366&rft.eissn=1530-0366&rft.spage=101332&rft_id=info:doi/10.1016%2Fj.gim.2024.101332&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1530-0366&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1530-0366&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1530-0366&client=summon