TABLE 2.
List of ASD-related chromosomal and monogenic disorders that have been reported co-presented with auditory dysfunction.
| Chromosomal/genetical abnormalities | Map position | Incidence | Manifestations | Potential related genes and function | References | |
| Chromosomal disorder | chromosomal 13q12→q13 deletion | • deletion at the distal third of band 13q12 • deletion at the proximal two-thirds of band 13q13 | / | • auditory processing defects • autism spectrum disorder • language deficit | • NBEA: 1) encodes a neuron-specific multidomain protein 2) functions as a protein kinase anchor protein 3) post-Golgi neuronal membrane trafficking • MAB21L1: neural development • DCAMKL1: 1) encodes a brain-specific transmembrane kinase 2) cortical development • DCX: 1) encodes doublecortin, a brain-specific putative signaling protein 2) neuronal migration • MADH9: a member of the SMAD family 1) mediate the TGF beta signaling pathway 2) proliferation and differentiation of many different cell types 3) synaptic junction differentiation |
Smith et al., 2002 |
| 16p11.2 deletions and duplications | heterozygous deletions and duplications of 16p11.2 | 1% of individuals with autism | • auditory dysfunction: 1) hearing loss 2) absence of acoustic startle responses • autism spectrum disorder • developmental delays, speech delay • obesity (deletion) and low body weight (duplication) • intellectual impairment • psychiatric disorders • seizures, syringomyelia • cardiac defects • motor hypotonia • immune deficiency |
• KCTD13: • encodes the polymerase delta-interacting protein 1 (PDIP1) • regulation of cell cycle during neurogenesis • SEZ6L2: epilepsy and language disorders • MAPK3: 1) a member of the MAP kinase family 2) cellular proliferation, differentiation, and cell cycle • NRX1, NRXN3: synaptic transmission and cell-cell interaction • CHD8, EHMT1, MECP2, SOX5, TBF4, SATB2, FOXP1: chromatin modifiers and transcription factors • FMR1 and CEP290: intellectual disability |
Yang et al., 2015 | |
| chromosome 8q22.2-q22.3 deletion | deletion at chromosome 8q22.2-q22.3 | / | • bilateral hearing loss: hypoplastic auditory canals • autism spectrum disorder • macrocephaly • childhood seizure disorder • moderate intellectual disability • facial phenotype • congenital heart defect | • GRHL2: non-syndromic autosomal dominant deafness gene • VPS13B: the causative gene for Cohen syndrome • SPAG1: responsible for primary ciliary dyskinesia • RRM2B: encodes a small subunit of p53 mitochondrial DNA disorders and depletions • NCALD: neuronal signal transduction process | Sinajon et al., 2015 | |
| chromosome 2p11.2 deletion | homozygous deletion in 2p11.2 | / | • hearing impairment • autism spectrum disorder • intellectual disability • language delay • behavioral disturbances | • ELMOD3: involves in autosomal recessive non-syndromic deafness-88 (DFNB88) • CAPG: 1) member of actin regulatory proteins 2) cytoskeletal rearrangements regulation 3) involves in Rett syndrome • SH2D6: signal transduction of receptor tyrosine kinase pathways |
Lahbib et al., 2019 | |
| Chromosome 4q deletion and 7q duplication | • deletion of chromosome 4 • microduplication of chromosome 7 | / | • unilateral hearing impairment • autism spectrum disorder • multisystem malformation: 1) facial dysmorphism: microcephaly 2) ocular malformation: ocular hypertelorism; exophthalmos 3) auditory malformation: low-set ears 4) appendicular malformation: |
• SPATA5: 1) mitochondrial function (morphology and dynamics) 2) neuronal development 3) spermatogenesis • FGF2: 6) Angiogenesis 6) cell survival, division, differentiation, and migration 6) proliferation and survival of auditory neuroblast |
Wu et al., 2020a | |
| single palmar flexion crease; overlapping toes 6) cardiopulmonary system: discontinued cyanosis recurrent respiratory infections patent foramen ovale tracheobronchomalacia 6) nervous system: persistent falcine sinus with a thin corpus callosum |
• limb development • wound healing • tumor growth • NAA15: encodes a component of the Nat A Nacetyl-transferase complex, which tethering the complex to the ribosome for posttranslational modification of proteins • SMAD1: development of pulmonary hypertension • HHIP: development of lung malformation | |||||
| Monogenic disorder | Fragile X Syndrome | • FMR1 gene locates in Xq27.3 • FMR1 gene silencing by: • amplification of a CGG repeat • methylation of the promoter region |
1 in 1250 males and 1 in 2500 females | • hearing loss: 1) elevated cortical responses to sound stimuli 2) aberrant ABRs • autism spectrum disorder • cognitive impairments • seizures • aberrant dendritic spine morphology • enhancement of response to sensory stimuli |
• a modulator of mRNA translation • regulates synaptic proteins production | Rotschafer et al., 2015 |
| MEIS2(MRG1) | locates in chromosome 15q14 | / | • hearing loss • autism spectrum disorder | • encodes a homeodomain protein implicated as a transcriptional activator | Douglas et al., 2018 | |
| • atrial or ventricular septal defect | • cell proliferation | |||||
| • developmental delay | • development of inner ear in chickens | |||||
| • intellectual disability | • development of heart, brain, limb | |||||
| • short stature | • differentiation of various tissues and organs | |||||
| • cleft palate | ||||||
| • gastrointestinal, skeletal, limb, and skin abnormalities | ||||||
| ADNP syndrome | locates in chromosome 20 | 0.17% of individuals with autism | • mild hearing loss: > 10% of children • autism spectrum disorder | • regulates ion channels genes • regulates the protein translation process | Hacohen-Kleiman et al., 2019 | |
| • intellectual, motor, social, and speech delays/disabilities | • neural tube closure • associates with the cytoskeleton | |||||
| • synaptic plasticity • microtubule-dependent axonal transport | ||||||
| • dendritic spine formation | ||||||
| • brain development | ||||||
| • mental function |
CAPG, Capping Actin Protein, Gelsolin Like; CEP290, Centrosomal Protein 290; CHD8: Chromodomain Helicase Dna Binding Protein 8; DCAMKL1, Doublecortin Like Kinase 1; DCX, Doublecortin; EHMT1, Euchromatic Histone Lysine Methyltransferase 1; ELMOD3, Domain Containing 3; FGF2, Fibroblast Growth Factor-2; FMR1, Fmrp Translational Regulator 1; FOXP1, Forkhead Box P1; GRHL2, Grainyhead Like Transcription Factor 2; HHIP, Hedgehog Interacting Protein; KCTD13, Potassium Channel Tetramerization Domain Containing 13; MAB21L, Mab-21 Like 1; MADH9, Smad Family Member 9; MAPK3, Mitogen-Activated Protein Kinase 3; MECP2, Methyl-Cpg Binding Protein 2; NAA15, N-Alpha-Acetyltransferase 15; NBEA, Neurobeachin; NCALD, Neurocalcin Delta; NRX1, nucleoredoxin 1; NRXN3, neurexin 3; RRM2B, ribonucleotide reductase regulatory TP53 inducible subunit M2B; SATB2, SATB homeobox 2; SEZ6L2, seizure related 6 homolog like 2; SH2D6, SH2 domain containing 6; SMAD1, SMAD family member 1; SOX5, SRY-box transcription factor 5; SPAG1, sperm associated antigen 1; SPATA5, spermatogenesis associated 5; VPS13B, vacuolar protein sorting 13 homolog.
“/” means that information on the item is not available in the relevant research.