Expanding the reproductive organ phenotype of CHD7-spectrum disorder.
| Title: | Expanding the reproductive organ phenotype of CHD7-spectrum disorder. |
|---|---|
| Authors: | Nomakuchi TT; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Danowitz M; Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, USA.; Stewart B; Human Genetics Unit, University of Edinburgh, Edinburgh, Scotland, United Kingdom.; Leonard J; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Izumi K; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Krantz I; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Kolon TF; Division of Urology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Langdon D; Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, USA.; Skraban C; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Van Batavia J; Division of Urology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Zackai E; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Jiao K; Center for Biotechnology & Genomic Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.; Linn R; Division of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Alexander C; Division of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Zaontz M; Division of Urology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Vogiatzi MG; Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, USA.; Pyle LC; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Rare Disease Institute and Center for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA.; Department of Genomics and Precision Medicine, George Washington University, Washington, DC, USA. |
| Source: | American journal of medical genetics. Part A [Am J Med Genet A] 2023 May; Vol. 191 (5), pp. 1418-1424. Date of Electronic Publication: 2023 Feb 16. |
| Publication Type: | Case Reports; Research Support, N.I.H., Extramural; Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101235741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4833 (Electronic) Linking ISSN: 15524825 NLM ISO Abbreviation: Am J Med Genet A Subsets: MEDLINE |
| Imprint Name(s): | Publication: Hoboken, N.J. : Wiley-Blackwell; Original Publication: Hoboken, N.J. : Wiley-Liss, c2003- |
| MeSH Terms: | CHARGE Syndrome*/genetics ; Disorders of Sex Development*/genetics ; Cryptorchidism*; DNA Helicases/genetics ; Penis/abnormalities ; DNA-Binding Proteins/genetics ; Genital Diseases, Male ; Phenotype ; Genitalia ; Male ; Female ; Humans |
| Abstract: | CHD7 disorder is a multiple congenital anomaly syndrome with a highly variable phenotypic spectrum, and includes CHARGE syndrome. Internal and external genital phenotypes frequently seen in CHD7 disorder include cryptorchidism and micropenis in males, and vaginal hypoplasia in females, both thought to be secondary to hypogonadotropic hypogonadism. Here, we report 14 deeply phenotyped individuals with known CHD7 variants (9 pathogenic/likely pathogenic and 5 VOUS) and a range of reproductive and endocrine phenotypes. Reproductive organ anomalies were observed in 8 of 14 individuals and were more commonly noted in males (7/7), most of whom presented with micropenis and/or cryptorchidism. Kallmann syndrome was commonly observed among adolescents and adults with CHD7 variants. Remarkably, one 46,XY individual presented with ambiguous genitalia, cryptorchidism with Müllerian structures including uterus, vagina and fallopian tubes, and one 46,XX female patient presented with absent vagina, uterus and ovaries. These cases expand the genital and reproductive phenotype of CHD7 disorder to include two individuals with genital/gonadal atypia (ambiguous genitalia), and one with Müllerian aplasia.; (© 2023 Wiley Periodicals LLC.) |
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| Grant Information: | K08 CA248704 United States CA NCI NIH HHS; KL2 TR001879 United States TR NCATS NIH HHS; R01 HL095783 United States HL NHLBI NIH HHS; T32 GM008638 United States GM NIGMS NIH HHS |
| Contributed Indexing: | Keywords: CHARGE; CHD7; DSD; Kallmann syndrome |
| Substance Nomenclature: | EC 3.6.4.12 (CHD7 protein, human); EC 3.6.4.- (DNA Helicases); 0 (DNA-Binding Proteins) |
| SCR Disease Name: | Penis agenesis |
| Entry Date(s): | Date Created: 20230216 Date Completed: 20230410 Latest Revision: 20240502 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10501305 |
| DOI: | 10.1002/ajmg.a.63148 |
| PMID: | 36794641 |
| Database: | MEDLINE |
Case Reports; Research Support, N.I.H., Extramural; Journal Article