Table 4.
Genetic diagnosis of the 49 patients solved by clinical exome sequencing.
| Genetic diagnosis (MIM #)—gene (transcript) | Variant (cDNA and protein) | Inheritance | Class | Phenotype (gender) |
|---|---|---|---|---|
| KBG syndrome AD (MIM #148050)- ANKRD11 (NM_001256182) | c.3193 A > T, p.Lys1065* | NA | LP | GDD/ID_synd (M) |
| c.548_551delGCAT, p.Arg183Profs*44 | NA | LP | GDD/ID_synd (M) | |
| c.2765_2766del, p.Glu922Alafs*6 (x2) | DN (x2) | P | GDD/ID_synd (M); GDD/ID + epi (F) | |
| c.1903_1907delAAACA, p.Lys635Glnfs*26 | NA | LP | GDD/ID_synd (M) | |
| Mental retardation, AD 26 (MIM #615834)- AUTS2 (NM_001127231) | c.1298del, p.Leu433Profs*40 | DN | P | GDD/ID + micro/macro (M) |
| Noonan syndrome 7 AD (MIM #613706)- BRAF (NM_004333) | c.1738A > G, p.Asn580Asp | DN | P | GDD/ID_synd (F) |
| Intellectual developmental disorder, XL, syndrome, Snijders Blok type (MIM #300958)- DDX3X (NM_001193416) | c.508dupG, p.Ala170Glyfs*11 | DN | P | GDD/ID_isol (F) |
| Mental retardation, XL 90 (MIM #300850)- DLG3 (NM_021120) | c.2266 C > T, p.Arg756* | Mat | P | GDD/ID_isol (M) |
| Kleefstra syndrome 1 AD (MIM #610253)- EHMT1 (NM_024757) | c.2426 C > T, p.Pro809Leu (x2) | DN, NA | P | GDD/ID_synd (M) x2 |
| Rubinstein-Taybi syndrome 2 AD (MIM #613684)- EP300 (NM_001429) | c.1365delT, p.Val456Leufs*9 | DN | P | GDD/ID_synd (M) |
| c.4179delA, p.Tyr1394Thrfs*16 | DN | P | GDD/ID_synd (F) | |
| Intellectual developmental disorder, AD (MIM #618089)- FBXO11 (NM_001190274) | c.1480 C > T, p.Arg494* | NA | LP | GDD/ID_synd (M) |
| Otopalatodigital syndrome type 1 XL (OPD1; MIM# 311300)- FLNA (NM_001110556) | c.586 C > T, p.Arg196Trp | Mat | LP | ASD_synd (M) |
| Rett syndrome, congenital variant AD (MIM #613454)- FOXG1 (NM_005249) | c.301 C > T, p.Gln101* | DN | P | GDD/ID + micro/macro (F) |
| c.553 A > T, p.Ser185Cys | DN | P | GDD/ID_isol (M) | |
| Mental retardation, language impairment with/without autistic features, AD (MIM #613670)- FOXP1 (NM_001244810) | c.454delG, p.Glu152Asnfs*54 | NA | LP | GDD/ID_synd (M) |
| Epileptic encephalopathy, early infantile, 19, AD (MIM #615744)- GABRA1 (NM_000806) | c.268 G > C, p.Asp90His | DN | P | GDD/ID + epi (M) |
| Polydactily pre and postaxial, AD (MIM #174700 and #174200)- GLI3* (NM_000168) | c.3640 C > T, p.Gln1214* | NA | LP | GDD/ID_isol (M) |
| Simpson-Golabi-Behmel syndrome, type 1, AD (MIM #312870)- GPC3 (NM_001164617) | c.1228 C > T, p.Arg410* | DN | P | GDD/ID_synd (F) |
| Mental retardation, AD 6 (MIM #613970)- GRIN2B (NM_000834) | c.1451 G > A, p.Gly484Asp | DN | P | ASD + epi (F) |
| c.2406_2414del, p.His802_Lys805delinsGln | DN | LP | GDD/ID_synd (F) | |
| c.1562_1563dup, p.Val522Argfs*10 | NA | P | GDD/ID_isol (F) | |
| Cornelia de Lange syndrome 5, X-linked (MIM #300882)- HDAC8 (NM_018486) | c.808 C > T, p.Arg361* | DN | P | GDD/ID_synd (F) |
| Mental retardation, XL 1/78 (MIM #309530)- IQSEC2 (NM_001111125) | c.2665_2667delATC, p.Ile889del | DN | LP | GDD/ID_synd (F) |
| Arboleda-Tham syndrome AD (MIM #616268)- KAT6A (NM_006766) | c.4120 G > T, p.Glu1374* | NA | LP | GDD/ID_synd (F) |
| Liang-Wang syndrome AD (MIM #618729)- KCNMA1 (NM_002247) | c.2984 A > G, p.Asn995Ser | DN | P | GDD/ID_synd (F) |
| Kabuki syndrome 1, AD (MIM #147920)- KMT2D (NM_003482) | c.5269 C > T, p.Arg1757* | DN | P | GDD/ID_synd (M) |
| Poretti-Boltshauser syndrome AR (MIM #615960)- LAMA1(NM_005559) | c.6333dupA, p.Gln2112Thrfs*6; c.2893 G > A, p.Asp965Asn | I-Trans | P/LP | GDD/ID_synd (M) |
| Rett syndrome XL (MIM #312750)- MECP2 (NM_004992) | c.1163_1188del, p.Pro388Argfs*8 | DN | P | GDD/ID_isol (F) |
| c.808 C > T, p.Arg270* | DN | P | GDD/ID_isol (F) | |
| c.378-2 A > G | DN | P | GDD/ID_isol (F) | |
| Deletion of ex 3 and 4a | DN | P | GDD/ID_isol (F) | |
| Mental retardation, XL 98 (MIM #300912)- NEXMIF (NM_001008537) | c.3458dupA, p.Asn1153Lysfs*8 | NA | LP | GDD/ID_synd (F) |
| Sotos syndrome 2, AD (MIM #614753)- NFIX (NM_001271043) | c.52-16 G > A | DN | LP | GDD/ID_synd (M) |
| Sotos syndrome 1, AD (MIM #117550)- NSD1 (NM_022455) | c.5691 T > G, p.Cys1897Trp | NA | LP | GDD/ID_synd (M) |
| Niemann-Pick disease, type C1, D, AR (MIM #257220)- NPC1 (NM_000271) | c.352_353delAG, p.Gln119Valfs*8/c.2780 C > T, p.Ala927Val | I-Trans | P | Other NDD (F) |
| Epileptic encephalopathy, early infantile, 9, XL (MIM #300088)- PCDH19 (NM_001105243) | c.361 G > A, p.Asp121Asn | DN | P | GDD/ID + epi (F) |
| White-Sutton syndrome, AD (MIM #616364)- POGZ (NM_015100) | c.3118 G > A, p.Glu1040Lys | NA | LP | GDD/ID_isol (F) |
| Jansen de Vries syndrome, AD (MIM #617450)- PPM1D (NM_003620) | c.1458_1464delACATGAT, p.His487Leufs*2 | DN | P | Other NDD (M) |
| Macrocephaly/Autism syndrome AD (MIM #605309)- PTEN (NM_000314) | c.633 C > G, p.Cys211Trp | NA | LP | ASD + micro/macro (M) |
| Glass syndrome AD (MIM #612313)- SATB2 (NM_001172509) | c.1299 C > G, p.Tyr433* | NA | LP | GDD/ID_synd (F) |
| Epilepsy, generalized, with febrile seizures plus, type 2, AD (MIM #604403)- SCN1A (NM_001165963) | c.2672 G > A, p.Gly891Glu | S | LP | GDD/ID + epi (M) |
| Nicolaides-Baraitser syndrome AD (MIM #601358)- SMARCA2 (NM_003070.5) | c.1477_1479del, p.Lys493del | DN | LP | GDD/ID_synd (LP) |
| Lamb-Shaffer syndrome AD (MIM #616803)- SOX5 (NM_001261414) | c.1310 G > A; p.Arg437His | DN | LP | GDD/ID_isol (F) |
| Pitt-Hopkins syndrome AD (MIM #610954)- TCF4 (NM_001083962) | c.990 G > A, p.Ser330Ser | DN | P | GDD/ID + micro/macro (M) |
| Mental retardation AR 13 (MIM #613192)- TRAPPC9(NM_031466.6) | c.3103 C > T, p.Arg1035* (homozygous) | I-Trans | LP | GDD/ID + micro/macro (F) |
| Mental retardation, AD 22 (MIM #612337)- ZBTB18 (NM_205768.2) | c.1384_1385delinsTA, p.Leu462* | DN | P | GDD/ID + micro/macro (M) |
For the genetic diagnosis, MIM numbers are provided; AD autosomal dominant, AR autosomal recessive, XL X-linked. For the inheritance, DN de novo, I-Trans inherited in trans, NA not available. For the variant class, LP likely pathogenic and P pathogenic. For the phenotype: ASD Autism spectrum disorder, GDD/ID Global developmental delay/intellectual disability, Other NDDs Other neurodevelopmental disorders, epi epilepsy, isol isolated forms, micro/macro micro/macrocephaly, synd syndromic, F female, M male. x2 2 patients.
aFor the MECP2 exons 3 and 4 deletion the estimated genomic coordinates are chrX:(153248310-153295808)-(153298018-153357594).