Fig. 1: Genotype and facial phenotype of individuals with DEAF1-associated neurodevelopmental disorders (DAND).

a Structure of the DEAF1 precursor messenger RNA (pre-mRNA) [NM_021008.3] with light blue boxes indicating the 5′ and 3′ untranslated regions (UTRs) and dark blue boxes representing the coding region of exons 1 to 12, connected by lines indicating introns (not drawn to scale). b Structure of DEAF1 protein [NP_066288], including the DNA-binding and dimerization SAND ___domain, the zinc finger homology ___domain (ZnF) also involved in DNA-binding, nuclear localization signal (NLS), nuclear export signal (NES), and MYND ___domain. Distribution of (c) de novo heterozygous variants leading to autosomal dominant mental retardation 24 and (d) homozygous or compound heterozygous variants leading to autosomal recessive dyskinesia, seizures, and intellectual developmental disorder. The number of patients described with the depicted variant are indicated between parentheses if the variant was indentified in more than one case. Novel variants are indicated in bold. e Nonspecific facial dysmorphisms of individuals with pathogenic de novo DEAF1 variants (A–L) and biallelic DEAF1 variants (M–P), showing common characteristics as horizontal eyebrow, broad nasal tip, exaggerated Cupid’s bow, thick lower lip vermilion, and pointed chin: (A) individual with p.(Gly212Ser), at 20 years old (AD/1); (B) individual with p.(Thr213Pro), at 7 years old (AD/3); (C) individual p.(Leu214Val), at 14 years old (AD/4); (D) individual with p.(Leu214Pro), at 3 years old (AD/5); (E) individual with p.(Lys216Glu), at 10 years old (AD/6); (F) individual with p.(Lys216Asn), at 7 years old (AD/7); (G) individual with p.(Pro174_Gly222del), at 6 years old (AD/8); (H) individual with p.(Gly225Glu), at 5 years old (AD/9); (I) individual with p.(Ser236Gly), at 4 years old (AD/11); (J) individual with p.(Arg254del), at 25 years old (AD/13); (K) individual with p.(Leu272Ser), at 2 years old (AD/15); (L) individual with p.(Ala276Pro), at 14 years old (AD/17); (M) individual with p.(Asp369Alafs*51) and p.(Cys540Metfs*18), at 17 years old (AR/1); (N) individual with p.(Trp234*) and p.(Glu239Gly), at 16 years old (AR/3); (O) individual with p.(Arg224Gln) in homozygosity, at 10 years old (AR/4); (P) individual with p.(Arg224Gln) in homozygosity), at 2 years old (AR/5). Individuals with de novo variants may have high forehead and/or macrocephaly, while individuals with biallelic variants may have narrow forehead and microcephaly.