GenomeDx: The Next Generation of Genome-Wide Microarray Analysis

GenomeDx v.3.0 enables a high-resolution, genome-wide microarray analysis to evaluate for known as well as novel genomic deletion and duplication syndromes. The custom-designed oligonucleotide microarray utilizes 105,000 probes that are placed across the non-repetitive sequence of the genome and offers increased probe density and technical sensitivity. This table provides brief summaries of clinically relevant loci for which genomic loss or gain has been associated with a disease phenotype.
The loci are grouped and color-coded into 4 major categories, based on the clinical utility of these tests:
Well-established microdeletion/duplication syndromes with a high detection rate. Microdeletion/duplication syndromes with a lower detection rate. Newly recognized microdeletion/duplication syndromes. Single gene disorders only rarely caused by partial or complete gene deletion/duplication. These disorders are predominantly caused by mutations detectable by DNA sequencing. Autism susceptibility loci

Autism Susceptibility Loci Covered by the GenomeDx 105K array
LOCUS
16p13.2 6q23.3 12p13.33 7q31.32 3p26.3 7q35 11q13.4 1q42.2 7q36.3 15q12 6q16.3 17q21.32 Xq28 7q31.2

GENE
A2BP1 AHI1 CACNA1C CADPS2 CNTN4 CNTNAP2 DHCR7 DISC1 EN2 GABRB3 GRIK2 ITGB3 MECP2 MET

LOCUS
Xq13.1 Xp22.33 7q22.1 2p16. 13q21.32 10q23.3 7q22.1 22q13.33 2q31. 2q24.2 17q11.2 9q34.13 16p13.3 15q11.2

GENE
NLGN3 NLGN4X NPTX2 NRXN1 PCDH9 PTEN RELN SHANK3 SLC25A12 SLC4A10 SLC6A4 TSC1 TSC2/PKD1 UBE3A

All reported intrachromosomal gains or losses linked to autism susceptibility (see microdeletions/duplications on page 1)

Chromosomal and Single Gene Disorders Covered by the GenomeDx 105K array
DISORDER
1p36 deletion syndrome 1 q 2 1 m i c r o d e l e t i o n ( TA R ) 1q41-1q42 deletion 2p15 microdeletion 2q32.2-2q33 microdeletion 2q37 subtelomeric deletion click on OMIM number for more information about that disorder 

LOCUS
1q21.1

GENE

OMIM
607872 274000

1p36 1q41-1q42 2p15 2q32.2-2q33 2q37

Multiple Multiple Multiple Multiple S AT B 2 Multiple

608148 600430

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GenomeDx: The Next Generation of Genome-Wide Microarray Analysis
DISORDER
3q29 microdeletion/duplication 6p25 microdeletion 7q11 Williams-Beuren region duplication 8p23 microdeletion/duplication 9 q 3 4 s u b t e l o m e r i c d e l e t i o n sy n d r o m e 10q22-10q23 microdeletion 12q24.21 microduplication 13q32 deletion 14q11.2 deletion 14q22-14q23 deletion 15q11.2-15q13.1 microduplication 15q13.3 microdeletion 15q24 microdeletion 16p11.2 microdeletion/duplication (AUTS14) 16p11.2-16p12.2 microdeletion 16p13.1 microdeletion/duplication 17q21 microdeletion/duplication 22q11.2 microduplication 2 2 q 1 1 . 2 d i s ta l m i c r o d e l e t i o n 22q13.3 microdeletion Xp11.3 microdeletion A l a g i l l e sy n d r o m e A l p o r t sy n d r o m e Alpha thalassemia/mental reta r d a t i o n A n d r o g e n i n s e n s i t i v i t y sy n d r o m e Angelman syndrome Aniridia type 2 A x e n fe l d - R i e g e r sy n d r o m e A x e n fe l d - R i e g e r sy n d r o m e t y p e 1 Bannayan-Riley-Ruvalcaba sy n d r o m e B a s a l c e l l n e v u s sy n d r o m e , G o r l i n Sy n d r o m e Beckwith-Wiedeman syndrome Blepharophimosis, ptosis epicanthus inversus (BPE) B ra n c h i o - o t o - r e n a l Sy n d r o m e Bruton’s agammaglobulinemia Ca m p o m e l i c d y s p l a s i a C a t - e y e sy n d r o m e Charcot-Marie tooth disease C H A R G E sy n d r o m e C h r o n i c g ra n u l o m a t o u s d i s e a s e , X - l i n ke d Cleidocra n i a l d y s p l a s i a Congenital adrenal hypoplasia Co n g e n i t a l a d r e n a l h y p e r p l a s i a Congenital diagphra g m a t i c h e r n i a Co r n e l i a D e L a n g e sy n d r o m e Co w d e n sy n d r o m e C r i - d u - c h a t sy n d r o m e Cy s t i n o s i s D a n d y - Wa l ke r m a l fo r m a t i o n Diabetes insipidus, X-linked click on OMIM number for more information about that disorder 

LO C U S
3q29 6p25 7q11.32 8p23 9q34

GENE
PA K 2

OMIM
609425 601631 609757

Multiple ELN Multiple E H MT 1 Multiple Multiple ZIC2 Multiple Multiple Multiple Multiple Multiple Multiple Multiple Multiple MAPT Multiple BCR SHANK3 ZNF674 J AG 1 ACSL4 HBA1 / HBA2 AR UBE3A PAX6 FO X C 1 PITX2 PTEN P TC H 1 IGF2 FOXL2 E YA 1 BTK SOX9 CRKL PMP22 CHD7 CYBB RUNX2 NROB1 CYP21A2 NR2F2 NIPBL PTEN T E RT CTNS ZIC1/ZIC4 AVPR2

10q22.3-10q23.31 12q24 13q32 14q11.2 14q22.1-q23.1 15q11.2-q13.1 15 q 13 . 1 - 15 q 13 . 3 15q24 16p11.2 16p11.2-p12.2 16p13.1 17q21 22q11.2 22q11.2 22q13.3 Xp11.3 20p12.2 Xp22.3 16p13.3 Xq12 15q11.2-15q13.1 11p13 6p25 4q25 10q23.31 9q22.32 11p15 3q22.3 8q13.3 Xp22.1 17q24.3 22q11.21 17p11.2 8q12.2 Xp11.4 6p21.1 Xp21.2 6p21.32 15q26.2 5p13.1 10q23.31 5p15.2 17p13.3 3q24 Xq28

609637

608636

611913 610543 610443 608363 606232 300578 118450 301050 141750 300068 105830 106210 602482 180500 153480 109400 130650 110100 113650 300300 114290 115470 118220 214800 306400 119600 300200 119600 142340 122470 158350 123450 219800 220200 304800

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GenomeDx: The Next Generation of Genome-Wide Microarray Analysis
DISORDER
D i G e o r g e / Ve l o c a r d i o fa c i a l sy n d r o m e DiGeorge locus 2 D o s a g e - s e n s i t i ve s e x r e ve r s a l D o w n sy n d r o m e c r i t i c a l r e g i o n d u p l i c a t i o n D u a n e ra d i a l ra y sy n d r o m e Duchenne/Becker muscular dystrophy (large del/dup) Familial adenomatous polyposis/Gardner syndrome Fe i n g o l d sy n d r o m e G l yc e r o l k i n a s e d e fi c i e n c y Gonadal dysgenesis G o r l i n Sy n d r o m e G r e i g c e p h a l o p o l y sy n d a c t y l y Hereditary neuropathy with pressure palsies/ C h a r c o t - M a r i e - To o t h d i s e a s e , Ty p e 1 A ( C MT 1 A ) Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome Hemophilia A Hemophilia B Holoprosencephaly type 1 Holoprosencephaly type 2 Holoprosencephaly type 3 Holoprosencephaly type 4 Holoprosencephaly type 5 Holt-Oram syndrome-related microdeletion Infantile spasm sy n d r o m e , X - l i n ke d I n fa n t i l e s p a s m sy n d r o m e , X - l i n ke d Jacobsen syndrome Juvenile retinoschisis, X-linke d K a l l m a n n sy n d r o m e Langer-Giedion syndrome; Hereditary multiple exostoses (HME) Le r i - We i l l d y s c h o n d r o s t e o s i s Le s c h - N y h a n s y n d r o m e Lowe sy n d r o m e Marfa n sy n d r o m e MECP2 duplication mental retardation syndrome M i c r o p h t h a l m i a w i t h l i n e a r s k i n d e fe c t s M i c r o p h t h a l m i a w i t h c a t a ra c t t y p e 2 M i c r o p h t h a l m i a t y p e 3 , sy n d r o m i c M i l l e r - D i e ke r sy n d r o m e M o w a t - W i l s o n sy n d r o m e N a b l u s m a s k - l i ke fa c i a l sy n d r o m e N a i l - p a t e l l a sy n d r o m e Nephronophthisis N e u r o fi b r o m a t o s i s t y p e 1 Neurofibromatosis type 2 N o o n a n sy n d r o m e O c u l o c u ta n e o u s a l b i n i s m 2 Opitz sy n d r o m e O r n i t h i n e t ra n s c a r b a m y l a s e d e fi c i e n c y O ra l - fa c i a l - d i g i ta l syd r o m e t y p e 1 Pa l l i s t e r - K i l l i a n s y n d r o m e click on OMIM number for more information about that disorder 

LO C U S
22q11.2

GENE
TBX1 NEBL

OMIM
188400 601362 300018 605298 607323 310200 175100 164280 300474 480000 610828 175700 162500 146255 306700 306900 236100 157170 142945 142946 609637 142900 308350 308350 147791 312700 308700 150230 127300 300322 309000 154700 300260 309801 212550 206900 247200 235730 608156 161200 256100 162200 101000 176876 203200 300000 311250 311200 601803

10p13-10p14 Xp21.2 21q22.3 20q13.2 Xp21.2 5q22.2 2p24.3 Xp21.3 Yp11.3 9q22.32 7p14.1 17p11.2 10p14 Xq28 Xq27.1 21q22.3 2p21 7q36 18p11.3 13q32 12q24.21 Xp22.13 Xp21.3 11q23-11q25 Xp22.13 Xp22.31 8q24.11 Xp22.33/Yp11.32 Xq26.2 Xq25 15q21.1 Xq28 Xp22.2 14q23.1 3q26.33 17p13.3 2q22.3 8q21.3-8q22.1 9q33.3 2q13 17q11.2 22q12.2 12q24 15q13.1 Xp22 Xp11.4 Xp22.2 12p arm

NROB1 DSCR3 SALL4 DMD APC M YC N GK1 S RY P TC H 1 GLI3 PMP22 GATA3 F8 F9 TM E M 1 SIX3 SHH TG I F 1 ZIC2 TBX5 / TBX3 CDKL5 ARX Multiple RS1 KAL1 EXT1 / TRPS1 SHOX H P RT 1 OCRL FBN1 MECP2 HCCS SIX6 SOX2 PA FA H 1 B 1 ZEB2 Multiple LMX1B NPHP1 NF1 NF2 PTPN11 OCA2 MID1 OTC OFD1 Multiple

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GenomeDx: The Next Generation of Genome-Wide Microarray Analysis
DISORDER
Pe l i z a e u s - M e r z b a c h e r sy n d r o m e P s e u d o v a g i n a l p e r i n e o s c r o ta l hy p o s p a d i a s Po l y c y s t i c k i d n e y d i s e a s e Po t o c k i - S h a f fe r sy n d r o m e Po t o c k i - L u p s k i s y n d r o m e P ra d e r - W i l l i sy n d r o m e P ra d e r - W i l l i - l i ke sy n d r o m e Re n a l c y s t s a n d d i a b e te s sy n d r o m e Re t i n o b l a s t o m a Re t t sy n d r o m e R u b i n s te i n - Ta y b i sy n d r o m e S a e t h r e - C h o t z e n sy n d r o m e S e x r e ve r s a l , a u t o s o m a l S m i t h - M a g e n i s sy n d r o m e Sotos sy n d r o m e Speech language disorder Split-hand/foot malformation type 1 Split-hand/foot malfo r m a t i o n t y p e 3 S te r o i d s u l fa ta s e d e fi c i e n c y S t i c k l e r sy n d r o m e t y p e 1 S t i c k l e r sy n d r o m e t y p e 2 Sy n p o l y d a c t y l y To w n e s - B r o c k s sy n d r o m e Tr i c h o r h i n o p h a l a n g e a l sy n d r o m e t y p e 1 Tu b e r o u s s c l e r o s i s t y p e 2 Ulnar-mammary syndrome Van der Woude syndrome Wa a r d e n b u r g sy n d r o m e t y p e 1 Wa a r d e n b u r g sy n d r o m e t y p e 2 / Ti e t z sy n d r o m e WAGR syndrome W i l l i a m s - B e u r e n sy n d r o m e Wilms tumor Wolf-Hirschhorn syndrome X - l i n ke d h e t e r o ta x y X-linked lissencephaly X - l i n ke d l y m p h o p r o l i fe ra t i ve sy n d r o m e X - l i n ke d m e n ta l r e ta r d a t i o n M R X 2 1 X - l i n ke d M R w i t h g r o w t h h o r m o n e d e fi c i e n c y XIST deletion on ring X chromosomes Whole chromosome and segmental aneuploidies Subtelomeric rearrangements Pe r i c e n t r o m e r i c r e a r ra n g e m e n t s click on OMIM number for more information about that disorder 

LO C U S
Xq22.2 2p23.1 16p13.3 11p11.2 17p11.2

GENE
PLP1

OMIM
312080 607306 601313 601224 610883 176270 176270 137920 180200 312750 180849 101400 154230 182290 117550 602081 183600 600095 308100 108300 604841 186000 107480 190350 191100 181450 119300 193500 193510 194072 194050 194070 194190 306955 300067 308240 300143 300123 314670

SRD5A2 PKD1 EXT2 / ALX4 RAI1 SNRPN SIM1 HNF1B RB1 MECP2 CREBBP TWIST1 Multiple RAI NSD1 FO X P 2 SHFM1 FBXW4 STS COL2A1 COL11A1 H O X c l u s te r SALL1 TRPS1 TSC2 TBX3 IRF6 PA X 3 MITF PAX6 / WT1 ELN WT1 Multiple ZIC3 DCX SH2D1A IL1RAPL1 SOX3 XIST

15q11.2-15q13.1 6q16.3 17q12 13q14.2 Xq28 16p13.3 7p21.1 9p24.3 17p11.2 5q35.3 7q3.1 7q21.3 10q24.32 Xp22.31 12q13.11 1p21.1 2q31.1 16q12.1 8q24.12 16p13.3 12q24.21 1q32.2 2q36.1 3p14.1 11p13 7q11.23 11p13 4p16.3 Xq26.3 Xq23 Xq25 Xp21.3 Xq27.1 Xq13.2 All chromosomes 41 regions 43 regions

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