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Advanced Neurology Genetics of neurodevelopmental disorders in Mexico

Table 3. Other mutations identified with autosomal recessive inheritance
Gene, sequence, and mutation Inheritance/Status Type of mutation/OMIM Patients/Clinical Family
presentation
COLQ, exon 2, c. 109dup (p.Leu37Profs*97) AR/Heterozygous Pathogenic/MIM603034 1/Congenital
amyoplasia
BTD, exon 4, c. 1330G>C (p.Asp444His) AR/Heterozygous Pathogenic/MIM253260 2/Epilepsy 3
COQ8A, exon 13, c. 1532C>T AR/Heterozygous Pathogenic/MIM612016 1/Motor disorder
(p.Thr511Met)
PMM2, exon 5, c. 367C>T (p.Arg123*) AR/Heterozygous Pathogenic/MIM212065 1/ASD
CC2D2A, intron 33, c. 4179+1del AR/Heterozygous Pathogenic/MIM612285 1/Epilepsy
(Splice site)
UBA5, exon 11, c. 1111G>A (p.Ala371Thr) AR/Heterozygous Pathogenic, low penetrance/MIM617132 1/Epilepsy
ACADS, exon 6, c. 625G>A (p.Gly209Ser) AR/Heterozygous Benign (reportable)/MIM201470 3/ASD 1
ACADS, exon 5, c. 511C>T (p.Arg171Trp) AR/Heterozygous Benign (reportable)/MIM201470 1/Motor disorder
GALC, exon 7, c. 742G>A (p.Asp248Asn) AR/Heterozygous Benign pseudodeficiency allele 4 2
GALC, exon 15, c. 1685T>C (p.Ile562Thr) AR/Heterozygous/ Benign pseudodeficiency allele 5 4
Homozygous
Abbreviations: AR: Autosomal recessive; ASD: Autism spectrum disorder; MIM: Mendelian inheritance in man; ACADS: Acyl-CoA dehydrogenase
deficiency.

Table 4. Variants of uncertain significance in patients with clinical signs

No Gene, sequence, and mutation Inheritance/Status SHIFT PolyPhen‑2 Patients/ Relatives
Clinical form
16/17 DMXL2, exon 12, c. 2096T>C (p.Ile699Thr) AD – AR/Heterozygous cis Tolerated Benign 2 ASD Thyroiditis in
mother
16/17 DMXL2, exon 42, c. 8770C>A (p.His2924Asn) AD – AR/Heterozygous cis Likely to be tolerated 2 ASD Thyroiditis in
mother
18 ADAR, exon 2, c. 577C>G (p.Pro193Ala) AD – AR/Heterozygous Deleterious Probably 1 ASD
damaging
18 BRAF, exon 18, c. 2176C>T (p.Arg726Cys) AD/Heterozygous Probably disruptive 1 ASD
19 SCN8A, exon 11, c. 1519G>C (p.Glu507Gln) AD/Heterozygous Deleterious Benign 1 ASD
20 CHRNB1, exon 10, c. 1230_1244dup (p.Glu410_ AD/Heterozygous Splicing disruption 1 MD Hypermobility
Pro414dup) 1 ASD spectrum in
mother
12 ARHGEF15, intron 7, c. 1422-10A>G (intronic) AD/Heterozygous Splicing disruption 2 Epilepsy, ASD Addiction
9 RAF1, exon 2, c. 124_125delinsAT (p.Ala42Ile) AD/Heterozygous Not available Benign 1 ADHD Lentigines and
nevus
Note: The first two rows are VUS reported on the same homolog (variants in CIS) for the 1 time in 3 symptomatic patients.
st
Abbreviations: AD: Autosomal dominant; ASD: Autism spectrum disorder; MD: Motor disorder; AR: Autosomal recessive; ADHD: Attention deficit
hyperactivity disorder.
according to algorithmic and functional studies, could be diagnosed with ASD, exhibited a VUS in heterozygosity
correlated with the clinical profiles of the patients studied. in the pseudogene GALC. Both patients, who had normal
In only two cases (both presenting with dysmorphias), karyotypes, were candidates for further investigation using
VUS of recessive inheritance was found, but this does microarrays and other genetic techniques to enhance our
not account for the neurophenotypes observed in these understanding of their conditions.
patients. Patient 24 was clinically suspected of having CHARGE

One patient with pharmacoresistant epilepsy was Syndrome due to the manifestation of an NDD, thumb
found to carry a non-pathogenic variant in TANGO2; hypoplasia, iris coloboma, ear dysplasia, dental enamel
however, the heterozygous nature of this variant weakens dysplasia, and congenital heart disease. Diagnostic tests
its significance as a causal hypothesis. Another patient, targeting CHD7 and an additional 303 genes associated

Volume 3 Issue 2 (2024) 7 doi: 10.36922/an.3359