Case Report: A novel missense variant in ZC4H2, c.196C>T p.(Leu66Phe), is associated with a mild, ZC4H2-related X-linked syndromic intellectual disability (ZARD) phenotype
ZC4H2 is an X-linked gene that has emerged as critical for neural development, synaptic functioning, and gene regulation. We present an 11-month-old male who was evaluated for bilateral congenital vertical talus identified in the newborn period. Exome sequencing identified a hemizygous, missense var...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2025.1518782/full |
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| author | Ria Garg Ria Garg Wenying Zhang Wenying Zhang Julianne E. Hartmann Anne Slavotinek Anne Slavotinek |
| author_facet | Ria Garg Ria Garg Wenying Zhang Wenying Zhang Julianne E. Hartmann Anne Slavotinek Anne Slavotinek |
| author_sort | Ria Garg |
| collection | DOAJ |
| description | ZC4H2 is an X-linked gene that has emerged as critical for neural development, synaptic functioning, and gene regulation. We present an 11-month-old male who was evaluated for bilateral congenital vertical talus identified in the newborn period. Exome sequencing identified a hemizygous, missense variant in ZC4H2, NM_018684.4:c.196C>T p.(Leu66Phe), that affects the same amino acid residue as a previously reported, pathogenic ZC4H2 variant, c.197T>A p.(Leu66His). The variant was inherited from his mother, who had camptodactyly of the fifth fingers, and was also present in the maternal uncle who carried a diagnosis of cerebral palsy. The pathogenic missense variant in this family is located in the coiled-coil domain of the ZC4H2 protein. Although data remain scarce, missense variants in this domain may be associated with a milder, ZC4H2-associated rare disorder (ZARD) phenotype. |
| format | Article |
| id | doaj-art-ccf26ad85ccd41a2b8c32a291d114e4c |
| institution | OA Journals |
| issn | 2296-2360 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pediatrics |
| spelling | doaj-art-ccf26ad85ccd41a2b8c32a291d114e4c2025-08-20T02:16:44ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-04-011310.3389/fped.2025.15187821518782Case Report: A novel missense variant in ZC4H2, c.196C>T p.(Leu66Phe), is associated with a mild, ZC4H2-related X-linked syndromic intellectual disability (ZARD) phenotypeRia Garg0Ria Garg1Wenying Zhang2Wenying Zhang3Julianne E. Hartmann4Anne Slavotinek5Anne Slavotinek6Center for Development, Behavior, and Genetics, State University of New York Upstate Medical University, Syracuse, NY, United StatesDepartment of Pediatrics, Upstate Golisano Children’s Hospital, Syracuse, NY, United StatesDepartment of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDepartment of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesZC4H2 is an X-linked gene that has emerged as critical for neural development, synaptic functioning, and gene regulation. We present an 11-month-old male who was evaluated for bilateral congenital vertical talus identified in the newborn period. Exome sequencing identified a hemizygous, missense variant in ZC4H2, NM_018684.4:c.196C>T p.(Leu66Phe), that affects the same amino acid residue as a previously reported, pathogenic ZC4H2 variant, c.197T>A p.(Leu66His). The variant was inherited from his mother, who had camptodactyly of the fifth fingers, and was also present in the maternal uncle who carried a diagnosis of cerebral palsy. The pathogenic missense variant in this family is located in the coiled-coil domain of the ZC4H2 protein. Although data remain scarce, missense variants in this domain may be associated with a milder, ZC4H2-associated rare disorder (ZARD) phenotype.https://www.frontiersin.org/articles/10.3389/fped.2025.1518782/fullcontractureneurodevelopmental disordersgrowth and developmentZC4H2ZARD |
| spellingShingle | Ria Garg Ria Garg Wenying Zhang Wenying Zhang Julianne E. Hartmann Anne Slavotinek Anne Slavotinek Case Report: A novel missense variant in ZC4H2, c.196C>T p.(Leu66Phe), is associated with a mild, ZC4H2-related X-linked syndromic intellectual disability (ZARD) phenotype Frontiers in Pediatrics contracture neurodevelopmental disorders growth and development ZC4H2 ZARD |
| title | Case Report: A novel missense variant in ZC4H2, c.196C>T p.(Leu66Phe), is associated with a mild, ZC4H2-related X-linked syndromic intellectual disability (ZARD) phenotype |
| title_full | Case Report: A novel missense variant in ZC4H2, c.196C>T p.(Leu66Phe), is associated with a mild, ZC4H2-related X-linked syndromic intellectual disability (ZARD) phenotype |
| title_fullStr | Case Report: A novel missense variant in ZC4H2, c.196C>T p.(Leu66Phe), is associated with a mild, ZC4H2-related X-linked syndromic intellectual disability (ZARD) phenotype |
| title_full_unstemmed | Case Report: A novel missense variant in ZC4H2, c.196C>T p.(Leu66Phe), is associated with a mild, ZC4H2-related X-linked syndromic intellectual disability (ZARD) phenotype |
| title_short | Case Report: A novel missense variant in ZC4H2, c.196C>T p.(Leu66Phe), is associated with a mild, ZC4H2-related X-linked syndromic intellectual disability (ZARD) phenotype |
| title_sort | case report a novel missense variant in zc4h2 c 196c t p leu66phe is associated with a mild zc4h2 related x linked syndromic intellectual disability zard phenotype |
| topic | contracture neurodevelopmental disorders growth and development ZC4H2 ZARD |
| url | https://www.frontiersin.org/articles/10.3389/fped.2025.1518782/full |
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