Table 1. Genetic findings in patients with Vici syndrome.
Mutation nomenclature follows the recommended guidelines (www.hgvs.orf/mutnomen). Nucleotide numbering for KIAA1632 is based on GenBank Reference Sequence Number NM_020964.2 and denotes the adenosine of the annotated translation start codon as nucleotide position +1. The genotype in the original probands reported by Dionisi-Vici and colleagues1 (Family 1), is an implied genotype based on heterozygous EPG5 variants identified in the parents. Based on sequencing of cDNA derived from patient fibroblast cultures, the homozygous intronic variants identified in Patient 4.1 were predicted to result in a frameshift and premature stop codon insertion, p.Phe1604Glyfs*20. Further quantitative PCR (qPCR) and Western blot studies on tissue from this patient indicated the presence of an unstable or quickly-degraded polypeptide (data not shown). The heterozygous missense variants identified in Patient 6.1 in trans were absent from in-house exome data and from 372 control chromosomes.
| Family | Patient | Consanguinity | Variant 1 | Variant 2 | ||
|---|---|---|---|---|---|---|
| Nucleotide | Amino acid | Nucleotide | Amino acid | |||
| 1 | 1.1 | No | c.4588C>T | p.Gln1530* | c.5704dupT | p.Tyr1902Leufs*2 |
| 1.2 | No | c.4588C>T | p.Gln1530* | c.5704dupT | p.Tyr1902Leufs*2 | |
| 2 | 2.1 | No | c.2413-2A>G | - | c.6724delA | p.Met2242Cysfs*5 |
| 3 | 3.1 | No | c.1253-1G>T | - | c.5110-1G>C | - |
| 4 | 4.1 | Yes | c.4952+1G>A | p.Phe1604Glyfs*20 | c.4952+1G>A | p.Phe1604Glyfs*20 |
| 5 | 5.1 | Yes | c.3481C>T | p.Arg1161* | c.3481C>T | p.Arg1161* |
| 5.2 | Yes | c.3481C>T | p.Arg1161* | c.3481C>T | p.Arg1161* | |
| 6 | 6.1 | No | c.5835T>A | p.Cys1945* | c.1370T>C c.2351A>C |
p.Leu457Pro p.Gln784Pro |
| 7 | 7.1 | Yes | c.1007A>G | p.Gln336Arg | c.1007A>G | p.Gln336Arg |
| 8 | 8.1 | No | c.2575G>T | p.Glu859* | c.6232C>T | p.Arg2078* |
| 8.2 | No | c.2575G>T | p.Glu859* | c.6232C>T | p.Arg2078* | |
| 9 | 9.1 | Yes | c.4751T>A | p.Leu1584* | c.4751T>A | p.Leu1584* |
| 10 | 10.1 | No | c.2719-1G>A | - | c.6295dupA | p.Ser2099Lysfs*5 |
| 11 | 11.1 | Yes | c.6724delA | p.Met2242Cysfs*5 | c.6724delA | p.Met2242Cysfs*5 |
| 12 | 12.1 | No | c.6005_6006dupAG | p.Leu2003Serfs*30 | c.6112T>C | p.Cys2038Arg |
| 13 | 13.1 | Yes | c.4783C>T | p.Gln1595* | c.4783C>T | p.Gln1595* |
| 14 | 14.1 | Yes | - | - | - | - |
| 15 | 15.1 | No | - | - | - | - |