Phenotypic spectrum of the recurrent TRPM3 p.( Val837Met ) substitution in seven individuals with global developmental delay and hypotonia - Sorbonne Université Access content directly
Journal Articles American Journal of Medical Genetics Part A Year : 2022

Phenotypic spectrum of the recurrent TRPM3 p.( Val837Met ) substitution in seven individuals with global developmental delay and hypotonia

Matthew Lines
  • Function : Author
Paula Goldenberg
  • Function : Author
Ashley Wong
  • Function : Author
Siddharth Srivastava
Allan Bayat
Hanne Hove
  • Function : Author
Helena Gásdal Karstensen
Kwame Anyane-Yeboa
Jun Liao
  • Function : Author
Nan Jiang
  • Function : Author
Alison May
  • Function : Author
Edwin Guzman
  • Function : Author
Manuela Morleo
  • Function : Author
Stefano d'Arrigo
  • Function : Author
Claudia Ciaccio
Chiara Pantaleoni
Raffaele Castello
  • Function : Author
Shane Mckee
  • Function : Author
Jinfon Ong
  • Function : Author
Hana Zibdeh-Lough
  • Function : Author
Frederic Tran-Mau-Them
  • Function : Author
Boris Keren
  • Function : Author
Henri Margot
  • Function : Author
Thomas Voets
  • Function : Author
Joris Vriens
  • Function : Author
a Micheil Innes
  • Function : Author
David Dyment

Abstract

TRPM3 encodes a transient receptor potential cation channel of the melastatin family, expressed in the central nervous system and in peripheral sensory neurons of the dorsal root ganglia. The recurrent substitution in TRPM3 : c.2509G>A, p.(Val837Met) has been associated with syndromic intellectual disability and seizures. In this report, we present the clinical and molecular features of seven previously unreported individuals, identified by exome sequencing, with the recurrent p.(Val837Met) variant and global developmental delay. Other shared clinical features included congenital hypotonia, dysmorphic facial features (broad forehead, deep‐set eyes, and down turned mouth), exotropia, and musculoskeletal issues (hip dysplasia, hip dislocation, scoliosis). Seizures were observed in two of seven individuals (febrile seizure in one and generalized tonic–clonic seizures with atonic drops in another), and epileptiform activity was observed in an additional two individuals. This report extends the number of affected individuals to 16 who are heterozygous for the de novo recurrent substitution p.(Val837Met). In contrast with the initial report, epilepsy was not a mandatory feature observed in this series. TRPM3 pathogenic variation should be considered in individuals with global developmental delays, moderate–severe intellectual disability with, or without, childhood‐onset epilepsy.

Dates and versions

hal-04573253 , version 1 (13-05-2024)

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Cite

Matthew Lines, Paula Goldenberg, Ashley Wong, Siddharth Srivastava, Allan Bayat, et al.. Phenotypic spectrum of the recurrent TRPM3 p.( Val837Met ) substitution in seven individuals with global developmental delay and hypotonia. American Journal of Medical Genetics Part A, 2022, 188 (6), pp.1667-1675. ⟨10.1002/ajmg.a.62673⟩. ⟨hal-04573253⟩
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