| Autor: |
Ben-Mahmoud A; Hamad Bin Khalifa University., Kishikawa S; RIKEN BioResource Research Center., Gupta V; Hamad Bin Khalifa University., Leach NT; Laboratory Corporation of America Holdings., Shen Y; Harvard Medical School., Moldovan O; Hospital Santa Maria, Centro Hospitalar Universitário Lisboa Norte., Goel H; University of Newcastle., Hopper B; Forster Genetics-Hunter New England Local Health District., Ranguin K; CHU de Caen Normandie., Gruchy N; CHU de Caen Normandie., Maas SM; University of Amsterdam., Lacassie Y; Louisiana State University., Kim SH; University of London., Kim WY; Kent State University., Quade BJ; Harvard Medical School., Morton CC; Harvard Medical School., Kim CH; Chungnam National University., Layman LC; Augusta University., Kim HG; Hamad Bin Khalifa University. |
| Jazyk: |
angličtina |
| Zdroj: |
Research square [Res Sq] 2023 Mar 27. Date of Electronic Publication: 2023 Mar 27. |
| DOI: |
10.21203/rs.3.rs-2572736/v1 |
| Abstrakt: |
In an apparently balanced translocation t(7;12)(q22;q24)dn exhibiting both Kallmann syndrome (KS) and intellectual disability (ID), we detected a cryptic heterozygous 4.7 Mb del(12)(p11.21p11.23) unrelated to the translocation breakpoint. This new finding raised the possibility that KS combined with neurological disorder in this patient could be caused by gene(s) within this deletion at 12p11.21-12p11.23 instead of disrupted or dysregulated genes at the genomic breakpoints. Screening of five candidate genes at both breakpoints in 48 KS patients we recruited found no mutation, corroborating our supposition. To substantiate this hypothesis further, we recruited six additional subjects with small CNVs and analyzed eight individuals carrying small CNVs in this region from DECIPHER to dissect 12p11.21-12p11.23. We used multiple complementary approaches including a phenotypic-genotypic comparison of reported cases, a review of knockout animal models recapitulating the human phenotypes, and analyses of reported variants in the interacting genes with corresponding phenotypes. The results identified one potential KS candidate gene ( TSPAN11 ), seven candidate genes for the neurodevelopmental disorder ( TM7SF3 , STK38L , ARNTL2 , ERGIC2 , TMTC1 , DENND5B , and ETFBKMT ), and four candidate genes for KS with ID ( INTS13 , REP15 , PPFIBP1 , and FAR2 ). The high-level expression pattern in the relevant human tissues further suggested the candidacy of these genes. We propose that the dosage alterations of the candidate genes may contribute to sexual and/or cognitive impairment in patients with KS and/or ID. Further identification of point mutations through next generation sequencing will be necessary to confirm their causal roles. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
