TABLE 1.
Disease phenotypes associated with insertions (+/− deletions) at the Xq27.1 mutational hotspot. Genomic coordinates are based on the GRCh37/hg19 reference sequence.
| Disease phenotype | Additional phenotypic features | Insertion sequence | Insertion size and orientation | Genes contained in insertion | Additional accompanying rearrangements at Xq27.1 | References | ||
|---|---|---|---|---|---|---|---|---|
| X-linked hypoparathyroidism (OMIM: #307700) | N/A | 2p25.3 | ∼340 kb (Direct) | SNTG2 (partial) | ∼25 kb deletion | Bowl et al. (2005) | ||
| X-linked hypoparathyroidism (OMIM: #307700) | N/A | 2p25.3 (Chr2: 856,644-903,578) | ∼47 kb (Direct) | Non-coding DNA only | ∼1.5 kb deletion | Taylor et al. (2015) | ||
| 3 bp insertion | ||||||||
| X-linked congenital generalized hypertrichosis (OMIM: #307150) | N/A | 4q31.22-q31.23 (Chr4: 148,464,548-148,764,583) | ∼300 kb (Inverted) | PRMT9 (full) | 25 bp insertion | Zhu et al. (2011) | ||
| TMEM184C (full) | ||||||||
| ARHGAP10 (partial) | ||||||||
| EDNRA (partial) | ||||||||
| 7 bp deletion a | ||||||||
| X-linked congenital generalized hypertrichosis (OMIM: #307150) | Scoliosis, spina bifida | 5q35.3 (Chr5: 177,831,590-177,957,166) | ∼126 kb (Direct) | COL23A1 (partial) | ∼1.3 kb deletion | Zhu et al. (2011) | ||
| 124 bp insertion (from Xq28) | ||||||||
| 2 bp insertion | ||||||||
| X-linked congenital generalized hypertrichosis (OMIM: #307150) | Deafness, dental/palate anomalies | 6p21.2 (Chr6: 39,786,474-39,397,468) | ∼389 kb (Inverted) | KIF6 (partial) | 56 bp insertion (from 3q21.2) | DeStefano et al. (2013) | ||
| 14 bp insertion | ||||||||
| 2 bp deletion | ||||||||
| DAAM2 (partial) | ||||||||
| X-linked congenital bilateral ptosis (OMIM: %300,245) | N/A | 1p21.3 (Chr1: 97,886,267-98,006,168) | ∼120 kb (Direct) | DPYD (partial) | 7 bp duplication | Bunyan et al. (2014) | ||
| 427 bp duplication | ||||||||
| Bilateral anophthalmia and XX sex reversal | Neurological abnormalities, orbital teratoma | 9q21 | 640 kb (Direct) | TRPM3 (partial) | 4 bp inversion | Chou, (2012) | ||
| 4 bp deletion | ||||||||
| XX male sex reversal | N/A | 1q25.2—1q25.3 (Chr1: 180,243,986-181,017,783) | ∼774 kb (Direct) | ACBD6 (full) | 9 bp insertion | Haines et al. (2015) | ||
| XPR1 (full) | 4 bp deletion | |||||||
| KIAA1614 (full) | ||||||||
| STX6 (full) | ||||||||
| OVAAL (full) | ||||||||
| MIR3121 (full) | ||||||||
| LHX4 (partial) | ||||||||
| MR1 (partial) | ||||||||
| Charcot-Marie-Tooth neuropathy, X-linked recessive, 3 (OMIM: #302802) | N/A | 8q24.3 (Chr8:145,768,312–145,848,158) | ∼78 kb (Direct) | ARHGAP39 (partial) | 19 bp insertion (from 12q13.12) | Brewer et al. (2016) | ||
| 12 bp inversion | ||||||||
| 1 bp deletion | ||||||||
| 1 bp single nucleotide variant | ||||||||
| Rare X-linked recessive compound phenotype (genu varum, cubitus valgus, everted lips) | N/A | Xp22.33/Yp11.32 (ChrX: 628,417-733,365/ChrY: 578,417-683,365) | ∼105 kb (Direct) | Non-coding DNA only | N/A | Si et al. (2019) | ||
| Multiple congenital abnormalities | N/A | 9p22.3-9p22.2 (Chr9: 16,489,097-16,659,203) | ∼170 kb (Inverted) | BNC2 (partial) | 4 bp deletion a | Middelkamp et al. (2019) | ||
| X-linked congenital bilateral laryngeal abductor paralysis (Plott syndrome, OMIM: 308850) | N/A | 10q21.3 (Chr10: 65,948,754-66,352,777) | ∼404 kb (Inverted) | Non-coding DNA only | ∼10 kb deletion | Boschann et al. (2022) | ||
| 59 bp insertion (from 10q21.3) | ||||||||
| 7 bp insertion | ||||||||
| 2 bp insertion | ||||||||
a
Deletion has been inferred based on the reported coordinates of the insertion breakpoints.