c9332cfd72152702bc27b1d5ac41ff2f diagnostics-13-02259.pdf 7f932115ce321b300bf3433aa0c93a280e64ba3c diagnostics-13-02259.pdf f19ad737125d415dfd929246c380e4ad8ebbc04f1ae9e5b3e53f3b7da8657f11 diagnostics-13-02259.pdf Title: Contribution of Dynamic and Genetic Tests for Short Stature Diagnosing: A Case Report Subject: Genetic tests have led to the discovery of many novel genetic variants related to growth failure, but the clinical significance of some results is not always easy to establish. The aim of this report is to describe both clinical phenotype and genetic characteristics in an adult patient with short stature associated with a homozygous variant in disintegrin and metalloproteinase with thrombospondin motifs type 17 gene (ADAMTS17) combined with a homozygous variant in the GH secretagogue receptor (GHS-R). The index case had severe short stature (SS) (-3.0 SD), small hands and feet, associated with eye disturbances. Genetic tests revealed homozygous compounds for ADAMTS17 responsible for Weill–Marchesani-like syndrome but a homozygous variant in GHS-R was also detected. Dynamic stimulation with an insulin tolerance test showed a normal elevation of GH, while the GH response to macimorelin stimulus was totally flattened. We show the implication of the GHS-R variant and review the molecular mechanisms of both entities. These results allowed us to better interpret the phenotypic spectrum, associated co-morbidities, its implications in dynamic tests, genetic counselling and treatment options not only to the index case but also for her relatives. Keywords: short stature; genetics; macimorelin; GHS-R; ADAMTS; ADAMTS17 Author: Betina Biagetti, Irene Valenzuela, Ariadna Campos-Martorell, Berta Campos, Sara Hernandez, Marina Giralt, Noelia Díaz-Troyano, Emilio Iniesta-Serrano, Diego Yeste and Rafael Simó Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jul 4 05:35:07 2023 CEST ModDate: Tue Jul 4 05:36:59 2023 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1488791 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YWWVQQ+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 PJWKSK+VnURWPalladioL Type 1 Custom yes yes no 15 0 GYHBWP+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 HPCXTL+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 FOSLVY+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 SOSCBV+CMSY10 Type 1 Builtin yes yes no 32 0 BXZUUH+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 50 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 77 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 81 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 85 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 89 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 96 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 103 0 CAMXTK+EURM10 Type 1 Builtin yes yes no 114 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 126 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 130 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 134 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 138 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 145 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 152 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 171 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 175 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 179 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 183 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 190 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 202 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 206 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 210 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 214 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 221 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-09-26 03:08:43 CEST RepresentationInformation: diagnostics-13-02259.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-09-25 17:13:28 CEST Size: 1488791 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 376 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Ethical Statement Destination: subsection.2.1 Item: Title: Biochemical Assays Destination: subsection.2.2 Item: Title: Genetic Tests Destination: subsection.2.3 Item: Title: Dynamic Tests Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: Baseline Phenotype Destination: subsection.3.1 Item: Title: Genetics Tests Destination: subsection.3.2 Item: Title: Dynamic Tests Destination: subsection.3.3 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Contribution of Dynamic and Genetic Tests for Short Stature Diagnosing: A Case Report Author: Betina Biagetti, Irene Valenzuela, Ariadna Campos-Martorell, Berta Campos, Sara Hernandez, Marina Giralt, Noelia Díaz-Troyano, Emilio Iniesta-Serrano, Diego Yeste and Rafael Simó Subject: Genetic tests have led to the discovery of many novel genetic variants related to growth failure, but the clinical significance of some results is not always easy to establish. The aim of this report is to describe both clinical phenotype and genetic characteristics in an adult patient with short stature associated with a homozygous variant in disintegrin and metalloproteinase with thrombospondin motifs type 17 gene (ADAMTS17) combined with a homozygous variant in the GH secretagogue receptor (GHS-R). The index case had severe short stature (SS) (-3.0 SD), small hands and feet, associated with eye disturbances. Genetic tests revealed homozygous compounds for ADAMTS17 responsible for Weill Marchesani-like syndrome but a homozygous variant in GHS-R was also detected. Dynamic stimulation with an insulin tolerance test showed a normal elevation of GH, while the GH response to macimorelin stimulus was totally flattened. We show the implication of the GHS-R variant and review the molecular mechanisms of both entities. These results allowed us to better interpret the phenotypic spectrum, associated co-morbidities, its implications in dynamic tests, genetic counselling and treatment options not only to the index case but also for her relatives. 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