Table 2

Genetic and clinical data of probands with CNVs causing obesity and/or intellectual disability

Proband IDCNVGenomic interval (hg38)Gene(s)Size (kb)gnomAD region MAF SizePatho-genicityGene or CNV- associated disorderAge (years)SexBMI SDS for agePhenotype (other than obesity)Additional pathogenic obesity-associated variantsLeptin (ng/mL)Insulin (μIU/mL)Cortisol (μg/dL)
#2341q42.12 loss hmzchr1:224923245–225051803DNAH14128.560VUSPanventriculomegaly (CNV del), intellectual disability, hydrops fetalis, nonimmune2.4F9.4Slow learner, intellectual disability108109
#2381p31.3 loss hmzchr1:65532214–65592881LEPR60.670PMorbid obesity0.8F9.1382612
#2631p31.3 loss hmzchr1:65592634–65637041LEPR44.410PMorbid obesity1.8F8.4Delayed milestones, mental retardation274613
7q31.1 loss htzchr7:111337755–111407620IMMP2L69.87chr7:111209525–111532640 0.00004656 323 kbVUSAutism, epilepsy, intellectual disability, multiple congenital abnormalities (CNV loss), neurodevelopmental disorder (CNV dup)
#3431q43 loss htzchr1:240207914–240208747FMN20.830PIntellectual disability, mental retardation, short stature, premature ovarian failure (CNV), intellectual disability2.1F6.6Delayed milestones11710611
7q31.1 loss htzchr7:111180340–111569415IMMP2L389.080PAutism, epilepsy, intellectual disability, multiple congenital abnormalities (CNV loss), neurodevelopmental disorder (CNV dup)
#30410q21.3 loss htzchr10:66402469–66676594CTNNA3274.130VUSAutism spectrum disorder (CNV), cardiomyopathy3M7NA292510
#33410q25.3 loss htzchr10:115799104–116272282ATRNL1. GFRA1473.180VUSATRNL1: cognitive impairment, autism, dysmorphic features (CNV). GFRA1: Hirschsprung disease (CNV), central hypoventilation syndrome2.7F5Delayed milestones22195
#29912p13.31 loss htzchr12:9192171–9208382PZP16.21chr12:9172788–9215201 0.00004656 42.4 kbVUSAutism spectrum disorder, congenital heart disease, neurodevelopmental disorder, breast cancer early onset15F4Metrorrhagia, severe body ache402312
#35412q24.33 loss htzchr12:133210742–133234403ZNF268. ANHX23.660VUSZNF268: autism spectrum disorder, congenital heart disease0.7M1.6Frequent diarrheaLEPR (c.2396–2A>G)61915
7q22.2 loss htzchr7:101039237–101041145MUC171.91chr7:101034793–101041958 0.0005203 7.17 kbVUSAutism spectrum disorder
#27114q11.2 loss htzchr14:20350503–20357181PARP26.680VUSSchizophrenia, prostate cancer, breast cancer3.1M6Slow learner81119
#33916p13.3 loss htzchr16:4959295–4992063SEC14L532.77chr16:4958364–5031681 0.00004656 73.3 kbVUSAutism spectrum disorder13F5.5Intellectual disability, delayed puberty, polydactylyMKKS (c.775del. p.T259Lfs*21)143213
#34716p12.2 loss htzchr16:21510262–21728466OTOA. METTL9. IGSF6218.210POTOA: autism spectrum disorder, hearing loss (CNV). METTL9: cognitive impairment4F4.0Delayed milestones, memory loss42514
#29418p11.31 loss htzchr18:4233040–4421599DLGAP1. DLGAP1-AS5188.560VUSDLGAP1: obsessive-compulsive disorder (CNV), schizophrenia, autism spectrum disorder, developmental disorder11M5Poor vision, aggressive behaviorBBS2 (c.116A>G. p.K39R)615710
#30319p13.2 loss htzchr19:8904672–8906876MUC162.21chr19:8688936–9141019 0.00004656 453 kbVUSAutism spectrum disorder0.4M5NA52110
#24719p13.2 loss htzchr19:12398272–12431993ZNF443. ZNF79933.72chr19:12386649–12433971 0.0002328 47.3 kbVUSZNF799: autism spectrum disorder, Tourette syndrome6.5M4.5NA101017
#2442q11.2 loss htzchr2:97077521–97244014FAHD2B. ANKRD36166.490VUSANKRD36: autism spectrum disorder, psychosis22MPWS-like features, no facial hair311616
#2702q32.1 loss htzchr2:183023784–184276709NCKAP1. DUSP19. NUP351,252.930VUSNCKAP1: autism spectrum disorder4.1M8.4Sleep apnea, aggressive behavior, recurrent RTI22617
#2152q37.3 loss htzchr2:239281474–239282694HDAC41.22chr2:239281331–239282793 0.001498 1.46 kbVUSBrachydactyly, mental retardation1.1M6.5Sleep apnea, gastric problems238314
#21920p12.1 loss htzchr20:14867224–15009042MACROD2141.82chr20:14677820–15136935 0.00004656 459 kbVUSEarly-onset obesity (CNV dup); Kabuki syndrome, ADHD, schizophrenia (CNV loss)0.8M8.7Slow learner18187
  17q24.2 loss htzchr17:68145129–68515603ARSG. AMZ2. PRKAR1A. WIPI1. SLC16A6370.480VUSARSG: Usher syndrome, neurodevelopmental disorder. PRKAR1A: Carney complex (CNV)
#22422q12.3 loss htzchr22:32247382–32255353SLC5A47.970VUSADHD9.5M4.1Asthma, mild intellectual disability12126
7q31.1 loss htzchr7:111407385–111596185IMMP2L188.8chr7:111380309–111597224 0.00004656 217 kbPAutism, epilepsy, intellectual disability, multiple congenital abnormalities (CNV loss), neurodevelopmental disorder (CNV dup)
#2776p22.3 loss htzchr6:17754387–17781333KIF13A26.950VUSAutism spectrum disorder0.6F7Wakes up at night demanding food28928
4q35.1-q35.2gainchr4:186017165–186210660TLR3. FAM149A. CYP4V2193.50VUSTLR3: herpes simplex encephalitis/encephalopathy; immunodeficiency. FAM149A: pulmonary arterial hypertension. CYP4V2: Bietti crystalline corneoretinal dystrophy (CNV loss); retinitis pigmentosa
#2986p22.3 loss htzchr6:17893182–18021242KIF13A128.060VUSAutism spectrum disorder11F3.8Intellectual disability, hypothyroidism253111
15q21.1 gainchr15:45106503–45178335DUOX2. DUOXA1. DUOX1. SHF71.830VUSDUOX2: hypothyroidism.
DUOXA1: schizophrenia, hydrops fetalis.
DUOX1: intellectual disability, hypothyroidism
#2508p22 loss htzchr8:16098745–16164282MSR165.54chr8:16087944–16166408 0.001723 78.5 kbVUSSchizophrenia (CNV loss), Barrett esophagus/esophageal adenocarcinoma, prostate cancer0.9F3.7Mild intellectual disability, slow movements7210
#31610q26.13 gainchr10:121503759–121870059FGFR2. ATE1366.30VUSFGFR2: Apert syndrome (CNV dup), craniosynostosis.
ATE1: hearing impairment, tinnitus, atrioventricular septum defect
10.3F5.5Slow learner, bowlegs, poor visionBBS5 (c.668_671del. p.E223Afs*14)148611
#3334p16.3 loss htzchr4:3444014–3448310HGFAC4.30VUSAutism spectrum disorder19MBMI: 39Delayed milestones4510214
#3915q11.2-q13.1 loss htzchr15:23235221–26108349 (hg19)MKRN3. MAGEL2. NDN. NPAP1. SNRPN. SNURF. UBE3A. ATP10A2,873.10P15q11.2-q13.1 loss CNV, feeding difficulties in infancy, hypogonadism, intellectual disability, muscular hypotonia, truncal obesity, schizophrenia6.1F5.2Atrophied uterus and ovaries130368
#8715q11.2-q13.1 loss htzchr15:23996462–28544359 (hg19)NPAP1. SNRPN. SNURF. UBE3A. ATP10A. GABRB3. GABRA5. GABRG3. OCA2. HERC24,547.90P15q11.2-q13.1 loss CNV, feeding difficulties in infancy, hypogonadism, intellectual disability, muscular hypotonia, truncal obesity, schizophrenia22FBMI: 43No menarche, moderate intellectual disability28197
#32015q11.2-q13.1 loss htzchr15:22781870–26561186NIPA1. NIPA2. CYFIP1. TUBGCP5. GOLGA6L1. LOC102723534. GOLGA8S. MKRN3. MAGEL2. NDN. LOC105370733. NPAP1. SNRPN. SNURF. UBE3A. ATP10A. GABRB33,779.3200P15q11.2-q13.1 loss CNV, feeding difficulties in infancy, hypogonadism, intellectual disability, muscular hypotonia, truncal obesity, schizophrenia4.8M6.0PWS-like features, intellectual disability12287
5q23.2 gainchr5:127447531–127539157MEGF10. PRRC191.63chr5:127045431–127965806 0.00004902 920 kbVUSMEGF10: minicore myopathy, congenital myopathy, muscle weakness
#28216p11.2 loss htzchr16:29581926–30231884SPN. QPRT. C16orf54. ZG16. KIF22. MAZ. PRRT2. PAGR1. MVP. CDIPT. SEZ6L2. ASPHD1. KCTD13. TMEM219. TAOK2. HIRIP3. INO80E. DOC2A. C16orf92. FAM57B. ALDOA. PPP4C. TBX6. YPEL3. GDPD3. MAPK3. CORO1A. BOLA2B. SLX1A. SULT1A3. NPIPB13649.960P16p11.2 loss CNV, severe obesity, autism8F3.2Slow learner, delayed milestones18716
#33811p12 gainchr11:36592557–36957106RAG2. C11orf74364.550VUSRAG2: immunodeficiency (CNV), Omenn syndrome2M8.6Poor vision, delayed milestonesALMS1 (c.10972C>T. p.R3658*)12601
#31511q23.3 gainchr11:118077018–118152698TMPRSS4. SCN4B75.68chr11:118076058–118161781 0.00004902 85.7 kbVUSTMPRSS4: cerebral atrophy, autosomal recessive. SCN4B: atrial fibrillation2.6F7.2NA152510
#31316p13.3 gainchr16:43545–176835POLR3K. SNRNP25. MPG133.290VUSPOLR3K: Hypomyelinating leukodystrophy.
MPG: schizophrenia, colorectal cancer
5.2F5.5Intellectual disability, recurrent RTI115013
#29018q21.33 gainchr18:63641736–63659552SERPINB3. SERPINB417.820VUSSERPINB3: liver cirrhosis.
SERPINB4: diabetes MODY, autism spectrum disorder
17FSecondary amenorrhea319611
#32119q13.43 gainchr19:57477251–57491801ZNF772. ZNF41914.55chr19:57461161–57532262 0.00004902 71 kbVUSZNF419: autism spectrum disorder0.6F7.4NALEPR (c.2396–1G>T)261713
#3072p11.2 gainchr2:85302449–85322813TCF7L1. TGOLN220.360VUSTCF7L1: glaucoma, primary congenital (CNV), autism6.0M5.2Intellectual disability173411
4q35.1-q35.2 gainchr4:186017165–186210660TLR3. FAM149A. CYP4V2193.5chr4:185990671–186121496 0.00009804 131 kbVUSTLR3: herpes simplex encephalitis/encephalopathy, influenza-associated.
CYP4V2: Bietti crystalline corneoretinal dystrophy, retinitis pigmentosa.
TLR3: inflammatory bowel disease, schizophrenia
#3192q14.2 gainchr2:119195166–119810001STEAP3. DBI. TMEM37. CFAP221. TMEM177. PTPN4614.840VUSSTEAP3: hypochromic anemia.
PTPN4: Rett-like syndrome (CNV loss), autism spectrum disorder, neurodevelopmental disorder
5M4.4Delay in mental age, aggressive behavior912211
#28521q11.2 gainchr21:13251123–14109107POTED. LIPI857.990VUSLIPI: hypertriglyceridemia11M3.7NA304123
#27521q22.3 gainchr21:42259283–42296415ABCG137.130VUSAbnormal HDL cholesterol, autism spectrum disorder, heart diseaseFNAMKKS (c.775del.p.T259Lfs*21)29149
#34222q11.22 gainchr22:21955538–22110518TOP3B154.980PMild mental retardation, generalized overgrowth (CNV dup), intellectual disability, schizophrenia1.8F8.8Delayed milestonesLEP (c.-29+1G>C)21915
3q29 gainchr3:197791254–197875785LRCH384.53chr3:197791715–197915689 0.00009804124 kbVUSNeurodevelopmental disorder
#26622q11.22 gainchr22:21955538–22110518TOP3B154.980PMild mental retardation, generalized overgrowth (CNV dup), intellectual disability, schizophrenia4.4F6.1NA23268
#32922q11.22 gainchr22:21957088–22215308TOP3B258.220PMild mental retardation, generalized overgrowth (CNV dup), intellectual disability, schizophrenia2.8F8.3NA19268
#2054p13 gainchr4:42806238–43454858GRXCR1648.620VUSDeafness, dizziness1.6M5.3NA595
#2525q31.3 gainchr5:141332929–141341211PCDHGA1. PCDHGA28.280VUSPCDHGA2: Cardiovascular malformationM
#3325q32 gainchr5:149860860–149886410PDE6A25.55chr5:149629797–150001191 0.00009804 371 kbVUSRetinitis pigmentosa, Leber congenital amaurosis16M3.2Rudimentary external genitalia, autistic352710
  • ADHD, attention deficit hyperactivity disorder; chr, chromosome; del, deletion; dup, duplicate; hmz, homozygous; htz, heterozygous; MAF, minor allele frequency; MODY, maturity-onset diabetes of the young; NA, not available; P, pathogenic; RTI, respiratory tract infection.