Kleefstra syndrome: Recurrence in siblings due to a paternal mosaic mutation.

Autor: Jobic F; Reference Center for Rare Diseases, Amiens-Picardy University Hospital, Amiens, France., Lacot-Leriche E; Reference Center for Rare Diseases, Amiens-Picardy University Hospital, Amiens, France.; EA 7273 CRP-CPO, University of Picardy, Jules Verne, Amiens, France., Piton A; Laboratory of Genetic Diagnosis, Institut de Génétique Médicale d'Alsace, Hôpitaux Universitaires de Strasbourg, Strasbourg, France., Le Moing AG; Department of Child Neurology, Amiens-Picardy University Hospital, Amiens, France., Mathieu-Dramard M; Reference Center for Rare Diseases, Amiens-Picardy University Hospital, Amiens, France., Costantini S; Reference Center for Rare Diseases, Amiens-Picardy University Hospital, Amiens, France., Morin G; Genetics Laboratory, Amiens-Picardy University Hospital, Amiens, France., Jedraszak G; Genetics Laboratory, Amiens-Picardy University Hospital, Amiens, France.; EA 4666 HEMATIM - CURS, University of Picardy, Jules Verne, Amiens, France.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2021 Dec; Vol. 185 (12), pp. 3877-3883. Date of Electronic Publication: 2021 Aug 06.
DOI: 10.1002/ajmg.a.62448
Abstrakt: Kleefstra syndrome (KS) is a rare autosomic dominant genetic disorder caused by euchromatic histone methyltransferase 1 (EHMT1) alterations. Patients mainly present with moderate to severe intellectual disability, a severe delay in/or absence of speech, autism spectrum disorder, childhood hypotonia, neuropsychiatric anomalies, and distinctive dysmorphic features. Here, we report the cases of a male and a female, two younger siblings of three, with asymptomatic parents. An EHMT1 new mutation was identified. Both presented with a typical core phenotype. Some specific features were noted, such as macrocephaly (previously reported) and enuresis (not yet described). Parental analysis identified the mutation in the mosaic state in the father. Reverse phenotyping enabled us to highlight the pauci phenotype features of inguinal hernia, azoospermia, and possible behavioral disorders. This allowed us to adapt his follow-up and genetic counseling for the family. Our three reported cases provide a new description of KS with an intragenic EHMT1 mutation, whereas in the literature most reported cases have EHMT1 deletions. Moreover, in the areas of next-generation sequencing and trio techniques with parental segregation, it is important to remain cautious about disregarding variants based on an autosomal recessive hypothesis.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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