Limb disorders

Gene: POLL

Genomics England clinical team notes - Agree with red rating. Part of the critical region of a duplication identified in split hand/foot malformation; no direct evidence this is the causative gene

Created: 9 Sep 2018, 7:52 p.m.

CNV tag added

Created: 5 Apr 2018, 2:03 p.m.

Comment on list classification: Keeping red rating as it appears that phenotype is due to copy number variation (duplication) rather than SNVs. Also some evidence suggesting that although POLL is part of the duplicated regions in SHFM3 patients, it might be duplication of BTRC which is causative.

Created: 5 Apr 2018, 2:02 p.m.

Not associated with a disease in OMIM or Gene2Phenotype. PMID: 29263051 - two Chinese patients with Split hand/foot malformation with a 534kb microduplication at 10q24 encompassing TLX1, LBX1, BTRC and POLL, and a 600kb duplication with TLX1, LBX1, BTRC, POLL, and FBXW4 located. PMID: 28777841 (article in Chinese, abstract available in English) - 3 families with Split hand/foot malformationMicroarray and real-time PCR analysis has identified a duplication in all patients from pedigrees 1 and 3, which have spanned FKSG40, TLX1, LBX1, BTRC, POLL and FBXW4 (exons 6-9) and LBX1, BTRC, POLL and FBXW4 (exons 6-9) genes, respectively. A missense mutation of the TP63 gene, namely c.692A>G (p.Tyr231Cys), was found in two patients from pedigree 2. PMID: 27600068 - A 514 kb gain at 10q24.31-q24.32 (chr10:102,962,134-103,476,346, hg19) was identified using 6.0 Single nucleotide polymorphism (SNP) microarray, resulting in the duplication of nine genes, including BTRC and FBXW4. A detailed systematic review of literature and mapping of breakpoints using microarray data from all reported cases in PubMed and DECIPHER were conducted, and exon 1 of BTRC gene was identified as the critical region responsible for the SHFM3 phenotype. PMID: 16691619 - use different techniques to narrow down the SHFM3 (10q24) to a minimal 325 kb duplication containing two genes BTRC and POLL. Expression analysis of 13 candidate genes within and flanking the duplicated region shows that BTRC (present in three copies) and SUFU (present in two copies) are overexpressed in SHFM3 patients compared to controls.

Created: 5 Apr 2018, 10:01 a.m.

Mode of inheritance
Unknown

Publications

• 12913067
• 29263051
• 28777841
• 28422522
• 27600068
• 23596994
• 16691619

Mode of pathogenicity
Other