
PMID- 37940764
OWN - NLM
STAT- MEDLINE
DCOM- 20240713
LR  - 20240716
IS  - 1559-0100 (Electronic)
IS  - 1355-008X (Print)
IS  - 1355-008X (Linking)
VI  - 85
IP  - 1
DP  - 2024 Jul
TI  - Exome sequencing (ES) of a pediatric cohort with chronic endocrine diseases: a 
      single-center study (within the framework of the TRANSLATE-NAMSE project).
PG  - 444-453
LID - 10.1007/s12020-023-03581-7 [doi]
AB  - BACKGROUND: Endocrine disorders are heterogeneous and include a significant 
      number of rare monogenic diseases. METHODS: We performed exome sequencing (ES) in 
      106 children recruited from a single center within the TRANSLATE‑NAMSE project. 
      They were categorized into subgroups: proportionate short stature (PSS), 
      disproportionate short stature (DSS), hypopituitarism (H), differences in sexual 
      development (DSD), syndromic diseases (SD) and others. RESULTS: The overall 
      diagnostic yield was 34.9% (n = 37/106), including 5 patients with variants in 
      candidate genes, which have contributed to collaborations to identify 
      gene-disease associations. The diagnostic yield varied significantly between 
      subgroups: PSS: 16.6% (1/6); DSS: 18.8% (3/16); H: 17.1% (6/35); DSD: 37.5% 
      (3/8); SD: 66.6% (22/33); others: 25% (2/8). Confirmed diagnoses included 75% 
      ultrarare diseases. Three patients harbored more than one disease-causing 
      variant, resulting in dual diagnoses. CONCLUSIONS: ES is an effective tool for 
      genetic diagnosis in pediatric patients with complex endocrine diseases. An 
      accurate phenotypic description, including comprehensive endocrine diagnostics, 
      as well as the evaluation of variants in multidisciplinary case conferences 
      involving geneticists, are necessary for personalized diagnostic care. Here, we 
      illustrate the broad spectrum of genetic endocrinopathies that have led to the 
      initiation of specific treatment, surveillance, and family counseling.
CI  - (c) 2023. The Author(s).
FAU - Gippert, Sebastian
AU  - Gippert S
AD  - Division of Pediatric Endocrinology and Diabetes, Center for Pediatrics and 
      Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany and 
      Center for Rare Diseases, University Hospital Heidelberg, Heidelberg, Germany.
FAU - Wagner, Matias
AU  - Wagner M
AUID- ORCID: 0000-0002-4454-8823
AD  - Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, 
      Technical University of Munich, Munich, Germany.
AD  - Institute for Neurogenomics, Helmholtz Zentrum Munchen, Neuherberg, Germany.
FAU - Brunet, Theresa
AU  - Brunet T
AD  - Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, 
      Technical University of Munich, Munich, Germany.
AD  - Department of Pediatric Neurology and Developmental Medicine, Hauner Children's 
      Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
FAU - Berruti, Riccardo
AU  - Berruti R
AD  - Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, 
      Technical University of Munich, Munich, Germany.
FAU - Brugger, Melanie
AU  - Brugger M
AUID- ORCID: 0000-0002-6920-8550
AD  - Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, 
      Technical University of Munich, Munich, Germany.
FAU - Schwaibold, Eva M C
AU  - Schwaibold EMC
AUID- ORCID: 0000-0003-2708-9642
AD  - Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
FAU - Haack, Tobias B
AU  - Haack TB
AUID- ORCID: 0000-0001-6033-4836
AD  - Institute of Medical Genetics and Applied Genomics, University of Tuebingen, 
      Tubingen, Germany and Centre for Rare Diseases, University of Tuebingen, 
      Tubingen, Germany.
FAU - Hoffmann, Georg F
AU  - Hoffmann GF
AUID- ORCID: 0000-0002-6593-896X
AD  - Division of Pediatric Endocrinology and Diabetes, Center for Pediatrics and 
      Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany and 
      Center for Rare Diseases, University Hospital Heidelberg, Heidelberg, Germany.
FAU - Bettendorf, Markus
AU  - Bettendorf M
AUID- ORCID: 0000-0002-7988-0316
AD  - Division of Pediatric Endocrinology and Diabetes, Center for Pediatrics and 
      Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany and 
      Center for Rare Diseases, University Hospital Heidelberg, Heidelberg, Germany.
FAU - Choukair, Daniela
AU  - Choukair D
AUID- ORCID: 0000-0002-1631-3883
AD  - Division of Pediatric Endocrinology and Diabetes, Center for Pediatrics and 
      Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany and 
      Center for Rare Diseases, University Hospital Heidelberg, Heidelberg, Germany. 
      daniela.choukair@med.uni-heidelberg.de.
LA  - eng
PT  - Journal Article
DEP - 20231108
PL  - United States
TA  - Endocrine
JT  - Endocrine
JID - 9434444
SB  - IM
MH  - Humans
MH  - Child
MH  - *Endocrine System Diseases/genetics/diagnosis
MH  - Male
MH  - Female
MH  - *Exome Sequencing/methods
MH  - Child, Preschool
MH  - Adolescent
MH  - Cohort Studies
MH  - Infant
MH  - Chronic Disease
MH  - Exome/genetics
MH  - Genetic Testing/methods
PMC - PMC11246252
OTO - NOTNLM
OT  - Exome sequencing
OT  - TRANSLATE-NAMSE
OT  - chronic pediatric endocrine diseases
OT  - multidisciplinary case conferences
OT  - rare diseases
COIS- The authors have no competing interests.
EDAT- 2023/11/09 00:42
MHDA- 2024/07/14 01:43
PMCR- 2023/11/08
CRDT- 2023/11/08 23:27
PHST- 2023/07/24 00:00 [received]
PHST- 2023/10/18 00:00 [accepted]
PHST- 2024/07/14 01:43 [medline]
PHST- 2023/11/09 00:42 [pubmed]
PHST- 2023/11/08 23:27 [entrez]
PHST- 2023/11/08 00:00 [pmc-release]
AID - 10.1007/s12020-023-03581-7 [pii]
AID - 3581 [pii]
AID - 10.1007/s12020-023-03581-7 [doi]
PST - ppublish
SO  - Endocrine. 2024 Jul;85(1):444-453. doi: 10.1007/s12020-023-03581-7. Epub 2023 Nov 
      8.
