Supplementary online material 1. FISH results
FISH analysis in patient III.4 metaphases demonstrates a der (21) with subtelomeric probe 1q, normal chromosomes 1 (A) and normal chromosome 21 with
subtelomeric probe 21q (B). FISH analysis in patient III.3 metaphase shows der (1) with subtelomeric probe 21q, normal chromosomes 21 and chromosome
1 (C).
Supplementary online material 2. SNP-array results of patient III.4.
SNP-array analysis shows a 8.5 Mb duplication on chromosome 1q43q44 (A) and 6.8 Mb deletion on chromosome 21q22.2q22.3 (B) in patient III.4.
Supplementary online material 3. SNP-array results of patient III.3.
SNP-array analysis shows a 8.5 Mb deletion on chromosome 1q43q44 (A) and 6.8 Mb duplication on chromosome 21q22.2q22.3 (B) in patient III.3.
Supplementary online material 4: Disease causing genes included in the deleted and duplicated regions.
Disease causing genes included in the region 1q43q44
Gene
FH
OMIM ID
136850
Protein
Fumarate hydratase,
mitochondrial
Serologically defined colon
cancer antigen 8
RAC-gamma serine/threonineprotein kinase
Tissue specificity
Ubiquitous granular cytoplasmic
expression
General cytoplasmic and nuclear
expression in all tissues
In fetal tissues, highly expressed in
heart, liver and brain but not in kidney
SDCCAG8
613524
AKT3
603387
ZBTB18
608433
Zinc finger and BTB domaincontaining protein 18
Lymphoid tissues, testis, heart, brain,
skeletal muscle, and pancreas
COX20
614698
NLRP3
606416
Cytochrome c oxidase protein
20, mitochondrial
NACHT, LRR and PYD
domains-containing protein 3
Cytoplasmic expression in most
tissues
Predominantly expressed in
macrophages. Also expressed in
dendritic cells, B- and T-cells
Gene function
Involved in the pathway tricarboxylic acid cycle
Plays a role in the establishment of cell polarity
and epithelial lumen formation
Regulates many processes including metabolism,
proliferation, cell survival, growth and
angiogenesis
Transcriptional repressor that plays a role in
various developmental processes such as
myogenesis and brain development
Involved in the assembly of the cytochrome
oxidase complex
Plays a crucial role in innate immunity and
inflammation
Disease causing genes included in the region 21q22.2q22.3
Gene
RIPK4
OMIM ID
605706
TMPRSS3
605511
RSPH1
609314
Protein
Receptor-interacting
serine/threonine-protein kinase 4
Transmembrane protease serine
3
Radial spoke head 1 homolog
Tissue specificity
Evidence at protein level
Gene function
Involved in stratified epithelial development
Alpha-crystallin A chain
Expressed in many tissues including
fetal cochlea
Expressed in trachea, lungs, airway
brushings, and testes
In fetal tissues, expressed in brain,
liver and kidney
Expressed in eye lens
605705
Serine/threonine-protein kinase
SIK1
Nuclear and cytoplasmic expression
in most tissues
CSTB
601145
Cystatin-B
AIRE
607358
Autoimmune regulator
Selective cytoplasmic and nuclear
expression in squamous epithelia and
urothelium
Mainly expressed by medullary
thymic epithelial cells (mTECs)
Acts as a permissive factor for cochlear hair cell
survival and activation at the onset of hearing
Necessary for proper building of the axonemal
central pair and radial spokes
Hydro-lyase catalyzing the first step of the
transsulfuration pathway
Contributes to the transparency and refractive
index of the lens
Serine/threonine-protein kinase involved in
various processes such as cell cycle regulation,
gluconeogenesis and lipogenesis regulation,
muscle growth and differentiation
An intracellular thiol proteinase inhibitor
CBS
613381
Cystathionine beta-synthase
CRYAA
123580
SIK1
TSPEAR
612920
Thrombospondin-type laminin
G domain and EAR repeatcontaining protein
ITGB2
600065
Integrin beta-2
COL18A1
120328
Collagen alpha-1(XVIII) chain
COL6A1
120220
Collagen alpha-1(VI) chain
COL6A2
120240
Collagen alpha-2(VI) chain
Cytoplasmic expression in
megakaryocytes of bone marrow,
including a secreted positivity in
several tissues
Selective cytoplasmic and
membranous expression in immune
cells, mainly in lymphoid tissue and
bone marrow
Present in multiple organs with
highest levels in liver, lung and
kidney
Distinct positivity in connective tissue
and extracellular matrix
Distinct expression in connective
tissue with cytoplasmic expression in
Functions as a sensor of histone H3
modifications that are important for the
epigenetic regulation of gene expression
May play a role in development or function of
the auditory system
Cell adhesion molecular binding
COLA18A probably plays a major role in
determining the retinal structure as well as in the
closure of the neural tube
Collagen VI acts as a cell-binding protein
Collagen VI acts as a cell-binding protein
FTCD
606806
LSS
600902
Formimidoyltransferasecyclodeaminase
Lanosterol synthase
PCNT
605925
Pericentrin
several cell types, mainly adipocytes
and fibroblasts
Selective cytoplasmic expression in
hepatocytes and renal tubules
General cytoplasmic expression
Expressed in all tissues tested,
including placenta, liver, kidney and
thymus
Folate-dependent enzyme displaying both
transferase and deaminase activity
May regulate lens protein aggregation and
increase transparency through the production of
lanosterol
Plays a role in the microtubule network
formation