Table 2.
Involved genes
| Chromosome | Gene/OMIM number | Patient phenotype | Gene function | Resource | Mendelian inheritance |
|---|---|---|---|---|---|
| Deletion Nr. 1 | |||||
| 6 | FBXL4/605654 | mtDNA depletion syndrome (infantile encephalomyopathic type) | Coding for a member of the F-Box family (targeting substrates for degradation of cellular regulatory proteins) Maintenance of mtDNA %HI score 10.28 |
[31–33] | recessive |
| 6 | POU3F2/600494 | None described | POU domain transcription factor predominantly expressed in the CNS. Likely playing an important role in mammalian neurogenesis and neuronal migration in the neocortex, positive regulator of Schwann cell development, downstream target of SIM1 %HI score 15.18 |
[15–17, 34] | Unknown |
| 6 | PRDM13/616741 | North Carolina Macular Dystrophy (NCMD), no other neurologic phenotype described | Prdm transcription factor, neural specific direct target of Ptf1a, controlling balance of inhibitory and excitatory neurons in somatosensory circuits during neuronal development, Required to produce the right number of pax2+ neurons in the dorsal spinal cord by repressing excitatory cell fate %HI score 56.20 |
[25, 35, 36] | dominant for NCMD, otherwise unknown |
| 6 | CCNC/123838 | None described | Member of the cyclin family, Protein kinase in the RNA polymerase II complex, cell cycle regulator %HI score 2.44 |
[30, 37] | Unknown, Protein involved in pathogenesis of tumour development and Alzheimer disease |
| 6 | COQ3/605196 | None described | Encodes an O-Methyltransferase, involved in two steps of Ubiquinone (Coenzyme Q10) biosynthesis %HI score 40.90 |
[29, 38] | Unknown |
| Deletion Nr. 2 | |||||
| 6 | GRIK2/138244 | Intellectual disability; ASD; behavioural disorder, epilepsy, dystonia | Encodes for the glutamate receptor 6, excitatory neurotransmission in the brain %HI score 2.34 |
[5, 6, 9, 18, 22, 39] | recessive; susceptibility gene |
Deletion 1 of our patient encompasses 9 genes, including FBXL4, POU3F2, CCNC, USP45, PNISR, FAXC, TSTD3, COQ3 and PRDM13. Deletion 2 partially encompasses GRIK2 (details see text). In this table only genes are listed with a known function described in OMIM (www.omim.org) or PubMed (http://www.ncbi.nlm.nih.gov/pubmed). Haploinsufficiency score (%HI) is mentioned as given in the Decipher database. HI score: predicted probability of exhibiting haploinsufficiency. High ranks 0–10% more likely to exhibit haploinsufficiency, low ranks 90–100% [40]