Table 1.
Copy number variants spanning known IHH genes
| Gene | Chr | Start | End | Size | Zygosity | CNV type | Monogenic full gene | Monogenic Partial | Intragenic (N of exons) | Multi-genic | Inheritance | Dx | Gender |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ANOS1 | chrX | 2771923 | 9734102 | 6.9 MB | Hem | Deletion | No | No | No | Yes | De novo | KS | Male |
| ANOS1 | chrX | 2771923 | 8536514 | 5.7 MB | Hem | Deletion | No | No | No | Yes* | Unknown | KS | Male |
| ANOS1 | chrX | 6966863 | 8591808 | 1.6 MB | Hem | Deletion | No | No | No | Yes* | Unknown | KS | Male |
| ANOS1 | chrX | 7137374 | 8700325 | 1.5 MB | Hem | Deletion | No | No | No | Yes | X-linked | KS | Male |
| ANOS1 | chrX | 6966863 | 8700325 | 1.7 MB | Hem | Deletion | No | No | No | Yes | X-linked | KS | Male |
| ANOS1 | chrX | 8521895 | 8591808 | 69 KB | Hem | Deletion | No | No | Yes (7) | No | De novo | KS | Male |
| ANOS1 | chrX | 8521895 | 8591808 | 69 KB | Hem | Deletion | No | No | Yes (7) | No | Unknown | KS | Male |
| ANOS1 | chrX | 8521895 | 8700325 | 178 KB | Hem | Deletion | No | Yes | No | No | X-linked | KS | Male |
| ANOS1 | chrX | 8538442 | 8700325 | 161 KB | Hem | Deletion | No | Yes | No | No | X-linked | KS | Male |
| FGFR1 | chr8 | 29920430 | 39537842 | 9.6 MB | Het | Deletion | No | No | No | Yes | De novo | KS | Male |
| FGFR1 | chr8 | 37553171 | 42050826 | 4.4 MB | Het | Deletion | No | No | No | Yes | Unknown | KS | Male |
| FGFR1 | chr8 | 35401812 | 40555017 | 5.1 MB | Het | Deletion | No | No | No | Yes | Unknown | KS | Male |
| FGFR1 | chr8 | 36641744 | 39114959 | 2.4 MB | Het | Deletion | No | No | No | Yes | Unknown | nIHH | Male |
| FGFR1 | chr8 | 37553171 | 39142533 | 1.5 MB | Het | Deletion | No | No | No | Yes | Unknown | KS | Male |
| GNRHR | chr4 | 65155330 | 70391829 | 5.2 MB | het | Deletion | No | No | No | Yes | In trans with SNV | nIHH | Male |
| GNRHR | chr4 | 68610188 | 68621901 | 11 KB | Hom | Deletion | No | Yes | No | No | AR | nIHH | Male |
| GNRH1 | chr8 | 25278991 | 25282653 | 3.6 KB | Hom | Deletion | No | Yes | No | No | AR | nIHH | Male |
| SEMA3A | chr7 | 83587561 | 83824314 | 236 KB | Het | Deletion | Yes | No | No | No | Unknown | KS | Male |
| NDNF | chr4 | 119944487 | 126408858 | 6.4 MB | het | Deletion | No | No | No | Yes | Unknown | nIHH | Male |
| WDR11 | Chr10 | 115312639 | 124097792 | 8.7 MB | Het | Deletion | No | No | No | Yes | De novo | KS | Female |
| ANOS1 | chrX | 8521895 | 8591808 | 69913 | Het | Duplication | No | No | Yes (7) | No | Unknown | KS | Female |
| ANOS1 | chrX | 8521895 | 8591808 | 69 KB | Het | Duplication | No | No | Yes (7) | No | Unknown | nIHH | Mlale |
| ANOS1 | chrX | 8553210 | 8591808 | 38 KB | Het | Duplication | No | No | Yes (3) | No | Unknown | KS | Male |
| PROKR2 | chr20 | 5281748 | 5295120 | 13 KB | Het | Duplication | Yes (CN = 5)*** | No | No | No | Unknown | KS | Male |
| PROP1** | chr5 | 177419138 | 177573377 | 154 KB | Het | Duplication | No | No | No | Yes | Unknown | niHH | Female |
| NSMF | chr9 | 140218079 | 140396276 | 178 KB | Het | Duplication | No | No | No | Yes | De novo | KS | Male |
| IGSF10 | chr3 | 150804487 | 151176594 | 372 KB | Het | Duplication | No | No | No | Yes (CN = 4)*** | Unknown | nIHH | Male |
| KLB | chr4 | 39435732 | 39512578 | 76 KB | Het | Duplication | No | No | No | Yes* | Unknown | nIHH | Male |
| TBC1D20** | chr20 | 388596 | 480675 | 92 KB | Het | Duplication | No | No | No | Yes | AD | KS | female |
The table shows the IHH gene affected by CNVs; the chromosomal breakpoints that defined the detected CNV; the size of the CNVs; their zygosity; type of CNVs (deletions/duplications; monogenic full gene, monogenic partial, intragenic exonic, and multigenic).
Abbreviations: AD, autosomal dominant; AR, autosomal recessive; CNV, copy number variant; IHH, isolated hypogonadotropic hypogonadism; KS, Kallmann syndrome (ie, IHH with anosmia); nIHH, normosmic IHH.
*Indicates the genes that were partially disrupted by a breakpoint of multigenic CNVs; their inheritance pattern, the diagnosis (Dx) of the probands, and the gender of the probands affected by the CNVs.
** Genes associated with syndromic forms of IHH (PROP1 is associated with combined pituitary hormone deficiency and TBC1D20 with Warburg Micro syndrome).
*** The duplication of IGSF10 led to 4 copies of the gene (copy number/CN = 4) and the duplication of PROKR2 to 5 copies (CN = 5).