Genome Sequencing of Idiopathic Speech Delay

Figure 1

Inheritance pattern of variants in six probands, the severity of speech delay, and conservation of the missense variants. (a–f) Sanger validation and segregation analysis of variants. Sanger sequencing traces are shown for all individuals with DNA available. Pedigrees show circles/squares filled black for probands, all of whom had speech delay, or for parents with self-reported speech and/or language difficulties. Circles/squares filled white represent parents without self-reported speech and/or language difficulties. (a) Frameshift variant in SETD1A in proband 01 that was inherited from the father, who self-reported problems with speech, reading, learning, and cognition. (b) Frameshift variant in PPP1R7 in proband 02 that was inherited from the father, who did not self-report any speech-related problems. (c) Missense variant in NAA15 in proband 03, inherited from the mother, who did not self-report any speech/language difficulties. (d) Missense variant in SPTBN1 in proband 04. The variant was not present in the mother. (e) Missense variant in ARF3 in proband 05. (f) De novo stop-gain pLoF variant in KDR in proband 06. (g) Speech competence of the speech delay cohort, based on percentage consonants and vowels correct. The probands who carry a variant classified as (likely) pathogenic are highlighted. (h) Amino acid evolutionary conservation of the relevant parts of proteins encoded by NAA15, SPTBN1, and ARF3. The arrows point to the amino acids affected by missense variants, each of which is highly conserved across diverse vertebrate species.

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)