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. 2023 May 18;110(6):998–1007. doi: 10.1016/j.ajhg.2023.04.010

Table 1.

Genotypes and corresponding phenotypes in individuals with ultra-rare POU3F2 variants identified by exome/genome sequencing

ID 1.1 ID 1.2 ID 2 ID 3 ID 412 ID 5.1a ID 5.2a ID 6 ID 7b ID 8 ID 9 ID 10
Genotype
Inheritance maternal unknown de novo de novo de novo paternal unknown de novo de novo de novo unknown de novo
Zygosity het het het het het het het het het het het het
Coding position c.135C>A c.135C>A c.914A>G c.41C>T c.812A>T c.664C>T c.664C>T c.929G>C c.1249_1252del c.1064G>T c.1325T>C c.1212C>A
Protein position p.Tyr45∗ p.Tyr45∗ p.Gln305Arg p.Ser14Phe p.Glu271Val p.Pro222Ser p.Pro222Ser p.Arg310Thr p.Gly417Leufs∗71 p.Arg355Leu p.Val442Ala p.Asn404Lys
MAF (gnomAD) 0 0 0 0 0 0 0 0 0 0 9.78 × 10−6 0
CADD PHRED 34.0 34.0 28.6 22.9 31.0 20.0 20.0 29.7 33 32.0 28.8 29.6
Affecting POU-protein domainsc yes yes yes no yes no no yes no yes no yes
Phenotype
Sex male female male male female male male male male male male male
Age (current) 33 years 62 years 9 years 4 years 10 years 8 years >30 years 20 years 16 years 14 years 11 years 15 years
1st manifestation infancy unknown postnatal toddler infancy infancy unknown infancy infancy infancy infancy infancy
Intellectual disability yes no yes yes yes no no no yes yes yes yes
ASD symptoms yes no yes yes yes no no no no yes yes yes
Neurodevelopmental delay yes no yes yes yes yes yes yes yes yes yes yes
Obesity yes yes yes no no no no yes yes yes Yes yes
(BMI [kg/m2]) (43; 29 years) (47; 60 years) (25; 6 years) (14; 4 years) (15; 8 years) ND ND (33; 15 years) (36; 15 years) (35; 13 years) (34; 10 years) (54; 14 years)
Hyperphagia yes yes yes no no no no yes no yes yes yes
Diabetes yes yes no no no no no no no no no no
Morphological CNS anomaly ND ND brain MRI normal ND brain MRI normal leuko-encephalopathy leuko-encephalopathy brain MRI normal brain MRI normal ND ND microcephaly
Uro-renal anomalies CAKUT: hydro-nephrosis no no no no CAKUT: ureter duplex, dysplastic kidneys neurogenic bladder no no no no no

The variants reported refer to GenBank: NM_005604.4. Abbreviations: ACMG, American College of Medical Genetics and Genomics; ASD, autism spectrum disorder; CADD, Combined Annotation Dependent Depletion (v1.4); CAKUT, congenital anomalies of the kidney and urinary tract; CNS, central nervous system; het, heterozygous; MAF, minor allele frequency; MRI, magnetic resonance imaging; ND, no data.

a

Additional variant in COL4A2 (GenBank: NM_001846.3): c.315+1G>C, splice site analysis confirmed pathogenicity by exon skipping.

b

Additional variant in KDM3B (GenBank: NM_016604.3): c.5191G>A (p.Glu1731Lys).14