Table 3.
Recurrent and Overlapping Loci in ASD
Chromosome | FamID | Sex | Typea | Size (bp)b | CNV | Origin | Genesc | Phenotype Comments | |
---|---|---|---|---|---|---|---|---|---|
1 | 2q14.1 | SK0147-003 | F | SPX | 478,370 | loss | paternal | DPP10 exonic | IQ/LOFd unknown, RL/ELe sev delay, RB2+,f dysmorph 3+,g neurofibromatosis type 1, abnormal EEG |
SK0288-003 | F | SPX-MZ | 105,120 | gain | paternal | DPP10 intronic | IQ/LOF 73, RL/EL average/mild delay, RB 2+, dysmorph N/A | ||
2 | 2q32.1 | SK0306-004 | F | SPX | 97,130 | loss | de novo | none | IQ/LOF 68, RL/EL mild delay, speech 2+,h RB2+, dysmorph 3+, severe hypotonia |
NA0030-000 | M | SPX | 112,323 | loss | maternal | none | IQ/LOF 69, RL/EL mod delay, RB2+, dysmorph 1+, seizures, medicated for OCD, motor incoordination | ||
3 | 6q22.31 | MM0220-003 | M | MPX | 318,000 | gain | paternal | PLN whole | IQ/LOF 82, language average, dysmorph 2+, high myopia, fine motor difficulties |
NA0025-000 | M | SPX | 293,989 | gain | paternal | PLN whole | IQ/LOF unknown, language: regression/mild delay, RB2+, dysmorph 0 | ||
4 | 7q36.2 | SK0190-003 | M | SPX | 1,780,000 | gain | maternal | DPP6 whole | IQ/LOF 55, RL/EL sev delay, speech 2+, RB1+, dysmorph N/A, parents 1st cousins |
SK0115-003 | M | SPX | 274,000 | gain | unknown | DPP6 exonic | IQ/LOF 86, RL/EL average, RB2+, ysmorph N/A, | ||
SK0058-003 | M | MPX | 16,788 | gain | maternal | DPP6 intronic | IQ/LOF 111, RL/EL average, RB1+, ysmorph N/A | ||
NA0002-000 | M | SPX | 66,462 | loss | de novo | DPP6 exonic | IQ/LOF unknown, RL/EL severe delay, RB3+, dysmorph 0 | ||
5 | 8q11.23 | SK0143-003 | M | SPX | 285,200 | gain | unknown | UNQ9433 whole, RB1CC1 exonic | IQ/LOF 65, RL/EL sev delay, speech 2+, RB2+, dysmorph 2+, seizures, hypoplastic left heart syndrome, left hemidiaphragm paralysis |
MM0236-004 | M | MPX | 271,679 | gain | unknown | RB1CC1 exonic | IQ/LOF 84, language average, RB1+, dysmorph 0, central auditory processing difficulty | ||
6 | 9p24.1 | SK0270-003 | M | SPX | 38,900 | loss | unknown | none | IQ/LOF 67, RL/EL mild/mod delay, speech 1+, RB3+, dysmorph N/A |
MM0103-003 | M | MPX | 34,950 | loss | paternal | none | IQ/LOF 100, language mild delay, speech 0, RB2+, dysmorph 0, twin preg (other twin lost in 1st trimester), premature (34 wks with respiratory distress syndrome), club feet | ||
7 | 11p12 | MM0272-003 | M | MPX | 262,938 | loss | maternal | none | IQ/LOF 74, language mild delay, speech 3+, RB2+, dysmorph N/A, seizures, unilateral congenital ptosis |
SK0167-003 | F | MPX | 192,846 | loss | unknown | none | IQ/LOF 62, RL/EL average/mild delay, speech apraxia 2+, dysmorph N/A | ||
8 | 13q21.32 | SK0023-003 | M | SPX | 189,438 | gain | unknown | PCDH9 intronic | IQ/LOF 82, RL/EL mod/sev delay, speech 2+, RB2+, dysmorph N/A; seizures |
MM0299-003 | F | MPX | 172,401 | gain | paternal | PCDH9 intronic | IQ/LOF 43, language nonverbal, RB2+, dysmorph 0, hypotonia, gags/chokes, fine motor delay | ||
9 | 15q11.2-q13.3 | SK0073-003 | F | CHR | 11,922,600 | gain | de novo | >50 genes | IQ/LOF 49, RL/EL mod delay, RB3+, dysmorph N/A, premature (34 wks) |
SK0245-005 | M | CHR | 11,871,747 | gain | de novo | >50 genes | IQ/LOF 47, RL/EL sev delay, RB3+, dysmorph N/A | ||
10 | 16p12.2 | MM0109-003 | F | SPX | 1,246,288 | gain | maternal | 8 genes | IQ/LOF 27, language nonverbal, RB3+, dysmorph 1+ |
MM0289-003 | F | MPX | 802,555 | loss | maternal | 5 genes | IQ/LOF 45, language delay, RB2+, dysmorph 0 | ||
11 | 16p11.2 | NA0133-000 | F | SPX | 525,319 | gain | maternal | 29 genes | IQ/LOF & language moderate delay, speech 2+, RB1+, dysmorph 0, early motor delay |
SK0102-004 | M | SPX | 432,600 | gaini | de novo | 24 genes | IQ/LOF 39, RL/EL sev delay, speech 2+, RB3+, dysmorph 2+, epilepsy, congenital diaphragmatic hernia | ||
MM0088-003 | F | MPX | 675,829 | loss | de novo | 32 genes | IQ/LOF 82, RL/EL mod delay, RB3+, dysmorph 1+ | ||
SK0019-004 | M | SPX | 675,829 | loss | de novo | 32 genes | IQ/LOF 93, RL/EL average, speech 2+, RB3+, dysmorph 1+, hyperphagia and severe obesity | ||
12 | 22q11.2 | SK0119-003j | M | MPX | 2,771,300 | loss | de novo | >50 genes | IQ/LOF 77, RL/EL mod/sev delay, dysmorph 3+, velocardiofacial syndrome |
SK0091-004 | F | MPX | 4,281,262 | gain | paternal | >50 genes | IQ/LOF 92, RL/EL average/mod delay, RB3+, dysmorph 0, placental insufficiency | ||
SK0297-003 | M | SPX-MZ | 4,281,262 | gain | de novo | >50 genes | IQ/LOF 74, language average; RB3+, dysmorph 2+, seizures, MZ twin (discordant for ASD) | ||
SK0323-003 | M | MPX | 743,100 | gain | unknown | 7 genes | IQ/LOQ 43, language sev delay, RB4+, dysmorph N/A | ||
13 | 22q13.31 | SK0123-004 | M | MPX | 601,528 | gain | maternal | none | IQ 93, language mod delay, RB4+, dysmorph 0, nonidentical triplet, Hirschsprung disease |
MM0102-003 | M | MPX | 80,380 | loss | maternal | none | IQ/LOF 60, language mild delay, dysmorph 0, weakness & hypotonia of arms |
Probands are ordered by chromosome location. Families are grouped based on simplex (SPX), multiplex (MPX), and chromosomal abnormalities (CHR). Simplex families with affected monozygotic twins are denoted as SPX-MZ. The de novo cases also appear in Table 2 and some of the family pedigrees are shown in Figure 2 and Figure S2.
All recurrent and overlapping CNVs were detected by the array validated with qPCR. The breakpoints have not been accurately defined, and CNVs may be smaller or larger than noted.
If the CNV intersects only a single gene (suggesting that it may disrupt the gene), the term “exonic” is used, and if the CNV encompasses the entire gene, the term “whole” is used. The term “intronic” is used for CNV that overlaps noncoding parts of a single gene.
IQ/LOF (level of functioning) denotes average of Vineland Social, Communication and daily living scores and nonverbal IQ, when available.
Language (RL, receptive language; EL, expressive language) was rated as average, nonverbal, or mild, mod (moderately), or sev (severely) delayed.
RB (repetitive behavior) score was derived from ADI and ADOS ratings (1+, mild; 2+, moderate; 3+, severe repetitive behaviors; or 0, no repetitive behaviors).
Dysmorphology scores were based on anthropometric measurement abnormalities and qualitative features documented either by a clinical geneticist or a developmental pediatrician. Anomalies were reviewed by a single clinical geneticist and assigned score 0, not dysmorphic; 1+, mild; 2+, moderate; 3+, severe degree of dysmorphism. Children with known genetic syndromes received a score of 3+. N/A, not assessed for dysmorphic features.
Speech refers to the severity of impaired speech intelligibility, most likely resulting from oral motor apraxia (1+, mild; 2+, moderate; 3+, severe unintelligibility).
CNV is called by only one algorithm.
SK0119-003 originally entered the study with an ASD diagnosis but upon re-examination after CNV detection was assessed to be below cutoffs for ASD.