This study Proband 1 | This study Proband 2 | Kloth et al, 2019 Proband 1 | Kloth et al, 2019 Proband 2 | |
Genotype | Homozygous | Homozygous | Homozygous | Compound heterozygous |
Chromosomal position (hg38) | chr15:66703842T>G; chr15:66703842T>G | chr15: 66 704 075G>A; chr15: 66 704 075G>A | chr15: 67073779T>C; chr15: 67073779T>C | chr15: 67073451T>A; chr15: 67073829T>C |
Nucleotide change | c.584T>G; c.584T>G | c.817G>A; c.817G>A | c.1397T>C; c.1397T>C | c.1069T>A; c.1447T>C |
Protein change | p.(Val195Gly); p.(Val195Gly) | p.[(Glu273Lys,Glu273Serfs*72)];[(Glu273Lys,Glu273Serfs*72)]) | p.(Ile466Thr); p.(Ile466Thr) | p.(Phe357Ile); p.(Ser483Pro) |
Type | Missense | Missense/splice-site | Missense | Missense; missense |
Protein domain | MH1 | MH1 | MH2 | MH2; MH2 |
CADD score (v1.6) | 31 | 35 | 28.8 | 31; 28.9 |
gnomAD (v2.1.1) | Absent | Absent | Absent | Absent |
Family history | Healthy parents | Healthy parents | Healthy parents | Healthy parents |
Consanguinity | Yes | Yes | Yes | No |
Sex | Male | Male | Male | Female |
Age at last follow-up | Early childhood | Early childhood | Middle childhood | Middle childhood |
Craniosynostosis | Metopic synostosis | Metopic synostosis | Absent | Absent |
Global developmental delay | Yes | No | Yes† | No |
Gross motor delay | Yes | No | Slightly delayed‡ | No |
Speech delay | Yes | No | Slightly impaired§ | No |
Cardiac and outflow tract abnormalities | No | No | Coarctation of the aorta | Dysplastic pulmonary valve, pulmonic stenosis, coronary artery stenosis (ie, left main coronary artery), pulmonary artery stenosis, dilated cardiomyopathy |
Radioulnar synostosis | Left-sided | Bilateral | Bilateral | Absent |
Other | Cryptorchidism, abnormal pulmonary vein morphology, factor XI deficiency, astigmatism | None | Facial dysmorphism (eg, microcephaly, abnormality of the ears, etc), unilateral renal hypoplasia, toe syndactyly (bilateral), dorsal hirsutism, EEG¶ abnormality | Facial dysmorphism (eg, low anterior hairline, prominent nose, short neck, abnormality of the ears, etc), transient neutropenia, decreased circulating antibody level |
Reference build, GRCh38; RefSeq NM_005585.5.
Human Phenotype Ontology (HPO) terms have been used to annotate the phenotypes mentioned in the table.
*Also associated with abnormal (p.(Glu273Serfs*72)) splicing, see text and figure 1C,D.
†With intellectual disability.
‡Sitting at 8 months, crawling at 10 months, walking at 19 months.
§Speaks 3–4 word sentences, uses fantasy language.
¶EEG, electroencephalography.