Table 1.
Variants in the Components of Notch Signaling Associated with Pubertal Disorders
| Variant | Reference | |||||||
|---|---|---|---|---|---|---|---|---|
| Gene (chromosome locus) | Nucleotide change | Protein change | Protein domain | Phenotype | Segregation | In silico prediction | No. of affected patients (index)/no. of total probands | |
| DLK1 (14q32) | ~14 kb deletion, including exon 1 | Truncated protein | – | CPP, overweight/obesity, glucose intolerance/type 2 DM, hypercholesterolemia | Sister and 2 paternal cousins HET, affected; Father HET, unaffected; Paternal grandmother HET, affected | – | – | Dauber et al16 |
| 479_479delC | Pro160Leufs*50 | EGF-like 4 | CPP, glucose intolerance, hypercholesterolemia | Paternal aunt HET, affected; Father affected, DNA not available | – | 1/31 | Gomes et al17 | |
| 594_594delC | Gly199Alafs*11 | EGF-like 5 | CPP, PCOS, infertility, early-onset type 2 DM, hepatic steatosis | Father HET, affected; Mother, paternal aunt and younger brother WT, unaffected; Sister HET, affected | – | 1/31 | Gomes et al17 | |
| 810_810delT | Val271Cysfs*14 | Juxta membrane | CPP, severe short stature | Father, and two paternal aunts affected, DNA not available; Son HET, unaffected (4 y old); Brother HET, affected | – | 1/31 | Gomes et al17 | |
| NOTCH1 (9q34) | 2333C > T | Thr778Ile | EGF-like 20 | nHH | Mother WT, unaffected | Deleterious ≥ 2 prediction programs | 1/48 | Quaynor et al20 |
| 25 kb duplication | – | – | CPP, hypotonia, developmental delay in motor, cognitive and communication skills, fleshy hands, minor dysmorphic features | N/A | – | – | Giannakopoulos et al21 | |
| JAG1 (20p12) | 323A >T | Asn108Ile | Near DSL domain (EC) | nHH | Father WT, unaffected; Sister WT, unaffected; Sister HET, nHH | Deleterious ≥ 2 prediction programs | 1/48 | Quaynor et al20 |
Abbreviations: CPP, central precocious puberty; DM, diabetes mellitus; DSL, Delta–Serrate–Lag2 domain; EC, extracellular; HET, heterozygous; N/A, not available; nHH, normosmic hypogonadotropic hypogonadism; PCOS, polycystic ovarian syndrome; WT, wild type.