David decided to stand still so I could
take his picture. Thanks David!
I often get asked to interpret a genetic report. I am not a clinician of any sort. I never even had a genetics course. But, there are certain skills one must pick up along the way to study which genes are missing in 22q13 deletion syndrome and what they do. So, I have some idea how to read a report, just enough to accomplish my goals.
If you have a genetic report, here are some ways you, too, can figure out which genes are missing. David only had a FISH test 15 years ago, so I don’t know how many genes he is missing. You may be in much better shape. If you had an array or sequence done on your child, you should have enough information to find out which genes are missing. Here is how.
The experts use the technical part of a genetic report to see what has been deleted. The technical part will often look something like this:
hg17 arr 22q13.33 (48,230,183-49,523,149) X1
This example is a simple terminal deletion of chromosome 22 (not a real case). It says that part of chromosome 22 only has one copy (X1). The nomenclature can get complicated if there are multiple genetic problems. The nomenclature is outlined here:
Once you know which base-pairs are missing (48,230,183-49,523,149) and which genome assembly was used to make the measurement (hg17), you can go to the UCSC Genome Browser and get gobs of information about the deletion. The Genome Browser is complicated to use, but I use it often.
Sometimes the report provides a complete list of the missing genes. “Complete” is relative to certain things. For instance, most gene array studies cannot detect the presence or loss of the last gene on the chromosome, RABL2B. This gene is too similar to RABL2A and no one thinks RABL2B is important enough to make a special effort to detect it. (I happen to disagree. See my blog Is 22q13 deletion syndrome a ciliopathy.) Otherwise, the gene list is useful. If the only listed genes are SHANK3 and ARSA, the gene list is worthless. It means the geneticist either did not want to look up, or share with you, the other genes that are missing.
End gene or deletion size
If the deletion is a terminal deletion, you can use the deletion size to look up the genes on my list (below). If the report says something like, “from PLXNB2 to ACR” or “distal to” PLXNB2, then you can find PLXNB2 on the list and it becomes the marker for where the deletion starts. Terminal deletions start from the “end” gene and go up the list (down in gene number on my list).
Go to the Foundation’s web site?
If you had 18q deletion syndrome, there is a site that was created for parents to look up the genes that are missing and what those genes do. No such site exists for 22q13.
Ask your geneticist
I have seen some very nice genetics reports with a complete list of genes deleted. This is rare, but you might try asking for such a document.
Here is a list of the genes that covers the last 9,300 Kb (9.3 Mb) of 22q13. That is about the size of the largest known terminal deletion. The list comes with a few caveats. First, deletions can be messy. Sometimes lots of genes are gone, then part of the subsequent gene is gone. People don’t count half a gene. They usually add the partial gene to the gene count. Micro arrays (gene chips) sample the genes every so many kilobases (Kb). It is not a continuous readout of the DNA. Thus, in most cases, you don’t know the exact position of the break. DNA includes many things in addition to genes. It encodes things called microRNAs, and the DNA has essential gene promoter, inhibitor and enhancer regions within genes and between genes. Thus, a gene list tells only part of the story. Finally, I found an error in my list this past week, so let me know, but please don’t complain if this has more errors! I will correct this page as I find errors. However, I emphasize that this list comes without any warranty whatsoever. I take no responsibility for its use. It is part of a blog to educate parents. It is not a tool for legal, medical or any other practice. Ok?
[updated/corrected 6 March 2016]
[updated/corrected 12 March 2016]
[updated/corrected 17 June 2016]
[updated/corrected 5 December 2016]
[updated/corrected 7 April 2017]
Table now shows the smallest distance to the gene. For example, a terminal deletion of size 196.0 Kbase will delete all the genes before ARSA and damage part of ARSA. Table is now limited to 9.3 Mbase (9,300,000) which is the largest recorded terminal deletion.
# Gene Deletion size (Kbase) 1 RABL2B 34.81 2 ACR 78.11 3 SHANK3 85.17 4 ARSA 195.14 5 MAPK8IP2 206.92 6 CHKB 235.47 7 CPT1B 240.05 8 SYCE3 255.56 9 KLHDC7B 267.45 10 ODF3B 286.65 11 TYMP 288.47 12 SCO2 292.86 13 NCAPH2 295.00 14 LMF2 310.78 15 MIOX 328.43 16 ADM2 332.03 17 SBF1 343.44 18 PPP6R2 373.38 19 DENND6B 491.41 20 PLXNB2 539.63 21 MAPK11 548.08 22 MAPK12 557.16 23 HDAC10 567.21 24 TUBGCP6 573.90 25 SELO 600.85 26 TRABD 618.90 27 PANX2 638.18 28 MOV10L1 656.85 29 MLC1 733.11 30 TTLL8 763.84 31 IL17REL 809.78 32 PIM3 854.39 33 CRELD2 895.76 34 ALG12 900.01 35 ZBED4 928.39 36 BRD1 995.26 37 C22orf34 1,160.96 38 FAM19A5 2,067.65 39 TBC1D22A 3,642.77 40 CERK 4,080.21 41 GRAMD4 4,180.53 42 CELSR1 4,281.30 43 TRMU 4,484.77 44 GTSE1 4,487.66 45 TTC38 4,543.18 46 PKDREJ 4,555.11 47 CDPF1 4,570.18 48 PPARA 4,620.06 49 PRR34 4,764.32 50 WNT7B 4,841.34 51 ATXN10 4,973.16 52 FBLN1 5,287.14 53 RIBC2 5,385.97 54 SMC1B 5,404.90 55 FAM118A 5,508.30 56 UPK3A 5,522.59 57 KIAA0930 5,577.70 58 NUP50 5,630.45 59 PHF21B 5,809.48 60 ARHGAP8 5,955.68 61 PRR5 6,080.79 62 LDOC1L 6,320.17 63 KIAA1644 6,505.62 64 PARVG 6,610.00 65 PARVB 6,649.55 66 SAMM50 6,821.94 67 PNPLA3 6,870.90 68 PNPLA5 6,926.46 69 SULT4A1 6,955.97 70 EFCAB6 7,248.33 71 MPPED1 7,310.62 72 SCUBE1 7,475.08 73 TTLL12 7,631.34 74 TSPO 7,655.23 75 MCAT 7,675.07 76 BIK 7,688.76 77 TTLL1 7,729.13 78 PACSIN2 7,942.26 79 ARFGAP3 7,961.07 80 A4GALT 8,123.48 81 ATP5L2 8,177.87 82 CYB5R3 8,173.96 83 RNU12 8,203.08 84 POLDIP3 8,203.60 85 SERHL2 8,260.06 86 RRP7A 8,298.67 87 SERHL 8,305.91 88 NFAM1 8,386.07 89 TCF20 8,603.03 90 CYP2D6 8,688.56 91 NDUFA6 8,727.69 92 SMDT1 8,735.12 93 FAM109B 8,739.03 94 NAGA 8,747.64 95 WBP2NL 8,785.70 96 SEPT3 8,828.88 97 CENPM 8,871.30 98 TNFRSF13C 8,891.65 99 SHISA8 8,903.80 100 SREBF2 8,911.16 101 CCDC134 8,992.58 102 MEI1 9,019.01 103 C22orf46 9,124.62 104 NHP2L1(SNU13)9,129.56 105 XRCC6 9,154.43 106 DESI1 9,197.37 107 PMM1 9,228.58 108 CSDC2 9,241.80 109 POLR3H 9,273.98 110 ACO2 9,289.48
Check out my earlier blogs (below) to learn how many of your friends are missing a similar number of genes and which genes might be important. If you find this information valuable, please leave me a positive comment, or repost the blog elsewhere (e.g., Facebook). Many thanks to each parent who has shared his/her child’s information and shared their own very personal stories. Your contributions and feedback helps me feel that I am not alone in the quest to make the world a better place for our kids.
How can the same deletion have such different consequences?
22q13 and the hope of precision medicine
22q13 Deletion Syndrome: hypotonia
Understanding gene size
Gene deletions versus mutations: sometimes missing a gene is better.
Is 22q13 deletion syndrome a ciliopathy?
Understanding translocations in 22q13 deletion syndrome: genetics and evolution
Understanding deletion size
Can 22q13 deletion syndrome cause ulcerative colitis?
Can 22q13 deletion syndrome cause cancer?
22q13 deletion syndrome – an introduction