Phenotypic and Genetic Insights Into CNOT3-Related Intellectual Developmental Disorder of Speech Delay, Autism, and Dysmorphic Faces (IDDSADF) From the First Two Japanese Cases.

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Τίτλος:	Phenotypic and Genetic Insights Into CNOT3-Related Intellectual Developmental Disorder of Speech Delay, Autism, and Dysmorphic Faces (IDDSADF) From the First Two Japanese Cases.
Συγγραφείς:	Ariyasu D; Department of Pediatrics, Kawasaki Municipal Hospital, Kanagawa, Japan., Kosaki R; Division of Medical Genetics, National Center for Child Health and Development, Tokyo, Japan., Cho H; Department of Pediatrics, Kawasaki Municipal Hospital, Kanagawa, Japan., Nakashima M; Department of Medical Genetics, NHO Tokyo Medical Center, Tokyo, Japan., Tsuchihashi T; Department of Pediatrics, Kawasaki Municipal Hospital, Kanagawa, Japan., Kosaki K; Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan., Yamazawa K; Department of Medical Genetics, NHO Tokyo Medical Center, Tokyo, Japan.
Πηγή:	American journal of medical genetics. Part A [Am J Med Genet A] 2026 Oct; Vol. 200 (10), pp. 2363-2369. Date of Electronic Publication: 2026 May 12.
Τύπος έκδοσης:	Case Reports; Journal Article
Γλώσσα:	English
Στοιχεία περιοδικού:	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-
Ιατρικοί όροι (MeSH):	Language Development Disorders/genetics , Language Development Disorders/pathology , Language Development Disorders/complications , Intellectual Disability/genetics , Intellectual Disability/pathology , Autistic Disorder/genetics , Autistic Disorder/pathology , Autistic Disorder/complications , Transcription Factors*/genetics, Japan/epidemiology ; Humans ; Child ; Male ; Female ; Phenotype ; Young Adult ; Mutation ; Exome Sequencing ; Face ; East Asian People
Περίληψη:	Intellectual Developmental Disorder with Speech Delay, Autism, and Dysmorphic Faces (IDDSADF) is a rare neurodevelopmental disorder caused by heterozygous variants in CNOT3. Although several cohorts have been documented worldwide, no Japanese patients have been reported to date. Here, we present the first two Japanese cases of IDDSADF, an 8-year-old girl and a 19-year-old boy, both presenting with developmental delay, characteristic facial features, and short stature. Both individuals exhibited a thin, tented upper lip, a morphology that has been rarely reported in other cohorts and may represent an ethnicity-associated trait. Growth impairment was observed either from early childhood or emerging after puberty and may represent an underrecognized aspect of the phenotype. Trio-exome sequencing identified pathogenic CNOT3 variants in both patients, including a recurrent frameshift (c.732dup, p.Ser245fs) and a novel splice-site substitution (c.837+1G>A). Our findings expand the phenotypic and mutational spectrum of IDDSADF, highlighting the importance of longitudinal auxological assessment and recognition of potential ethnicity-associated facial traits in its clinical diagnosis and management. (© 2026 Wiley Periodicals LLC.)
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Grant Information:	JP24ek0109760h0001 Japan Agency for Medical Research and Development; 21K19751 Japan Society for the Promotion of Science; 22H03048 Japan Society for the Promotion of Science; 25K02629 Japan Society for the Promotion of Science
Contributed Indexing:	Keywords: CNOT3‐related neurodevelopmental disorder; IDDSADF; developmental delay; facial morphology; growth impairment
Substance Nomenclature:	0 (Transcription Factors)
Entry Date(s):	Date Created: 20260512 Date Completed: 20260903 Latest Revision: 20260904
Update Code:	20260904
DOI:	10.1002/ajmg.a.70198
PMID:	42117603
Βάση Δεδομένων:	MEDLINE

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ISSN:	1552-4833
DOI:	10.1002/ajmg.a.70198