A Japanese patient with Teebi hypertelorism syndrome and a novel CDH11 EC1 domain variant.

Autor: Kuroda Y; Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Kanagawa, Japan., Saito Y; Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Kanagawa, Japan., Enomoto Y; Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama, Kanagawa, Japan., Naruto T; Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama, Kanagawa, Japan., Kurosawa K; Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Kanagawa, Japan.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2024 Jan; Vol. 194 (1), pp. 94-99. Date of Electronic Publication: 2023 Aug 30.
DOI: 10.1002/ajmg.a.63386
Abstrakt: The gene CDH11 encodes cadherin-11, a Type II cadherin superfamily member that contains five extracellular cadherin (EC) domains. Cadherin-11 undergoes trans-dimerization via the EC1 domain to generate cadherin complexes. Compound heterozygous and homozygous loss-of-function CDH11 variants are observed in Elsahy-Waters syndrome (EWS), which shows characteristic craniofacial features, vertebral abnormalities, cutaneous syndactyly in 2-3 digits, genitourinary anomalies, and intellectual disability. Heterozygous CDH11 variants can cause Teebi hypertelorism syndrome (THS), which features widely spaced eyes and hypospadias. We report a THS patient with a novel CDH11 variant involving the EC1 domain. The patient was a 10-month-old male with normal developmental milestones, but had widely spaced eyes, strabismus, hypospadias, shawl scrotum, broad thumbs (right bifid thumb in x-ray), polysyndactyly of the left fourth finger, and cutaneous syndactyly of left third/fourth fingers. Exome sequencing identified a de novo heterozygous CDH11 variant (NM_001797.4:c.229C > T [p.Leu77Phe] NC_000016.9:g.64998856G > A). Clinical features were consistent with previously reported THS patients, but polysyndactyly, broad thumb, and cutaneous syndactyly overlapped phenotypic features of EWS. THS and EWS may represent a spectrum of CDH11-related disorders. Residue Leu77 in this novel CDH11 variant lines a large hydrophobic pocket where side chains of the partner cadherin-11 insert to trans-dimerize, suggesting that the cadherin-11 structure might be altered in this variant.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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