Table 5 A review of literature and databases on the variants of the GLRA2 gene

NM_002063.4(GLRA2):c.16C > G

Missense

p. val6leu

Pathogenic

Autism Spectrum Disorder

N/R^a

N/R

N/R

Yes

Autism Spectrum Disorder

Iossifov (2014) Nature 515, 216 [34]

NM_002063.4(GLRA2):c.140T > C

Missense

p.Phe47Ser

Likely Pathogenic​

Not Provided

N/R

N/R

N/R

Global Developmental Delay, Seizure, Infantile Spasms, Nystagmus, Strabismus, Hyperactivity, Sleep Disturbance, Normal Interictal EEG

ClinVar (RCV001810525.1)

NM_002063.4(GLRA2):c.407A > G

Missense

p.Asn136Ser

Pathogenic

Intellectual Developmental Disorder, X-Linked, Syndromic, Pilorge Type

N/R

N/R

N/R

Yes

Autism Spectrum Disorder

Pilorge (2016) Mol Psychiatry 21, 936 [35]

NM_002063.4(GLRA2):c.458G > A

Missense

p.Arg153Gln

Pathogenic

Intellectual Developmental Disorder, X-Linked, Syndromic, Pilorge Type

N/R

N/R

N/R

Yes

Autism Spectrum Disorder

Pilorge (2016) Mol Psychiatry 21, 936[35]

NM_002063.4(GLRA2):c.718A > G

Missense

p.Lys240Glu

Likely Pathogenic

Autism Spectrum Disorder and Developmental Disorder

N/R

N/R

N/R

N/R

-

Chen X (2022) Front Mol Neurosci 15 [36]

NM_002063.4(GLRA2):c.777C > G

Missense

p.Ile259Met

Likely Pathogenic

Autism Spectrum Disorder

N/R

N/R

N/R

N/R

-

Marcogliese (2022), Cell Report 15;38 [37]

NM_002063.4(GLRA2):c.754C > T

Missense

p.Arg252Cys

Likely Pathogenic

Autism Spectrum Disorder

N/R

N/R

N/R

N/R

-

Marcogliese (2022), Cell Report 15;38 [37]

NM_002063.4(GLRA2):c.1049G > T

Missense

p.Arg350Leu

Pathogenic

Intellectual Developmental Disorder, X-Linked, Syndromic, Pilorge Type

N/R

N/R

N/R

Yes

Autism Spectrum Disorder

Piton A (2011) Mol Psychiatry 16 (8) [32]

NM_002063.4(GLRA2):c.862G > A

Missense

p.Ala288Thr

Likely Pathogenic

Not Provided

N/R

N/R

N/R

N/R

Seizure, Myoclonus, Cerebellar Ataxia, Developmental Regression

ClinVar (RCV001813918.1)

NM_002063.4(GLRA2):c.1199C > T

Missense

p.Pro400Leu

Likely Pathogenic

Not Provided

N/R

N/R

Yes

Yes

Seizure, Disorder of Language, Febrile Seizure (within the age range of 3 months to 6 years), Developmental Regression, Delayed Speech and Language Development, Anxiety, Obesity, Broad Face, Widow's Peak, Broad Eyebrow, Long Eyelashes, Prominent Eyelashes, Broad Nasal Tip, EEG Abnormality, Alpha-EEG

ClinVar(RCV001813921.1)

NM_002063.4(GLRA2):c.887C > T

Missense

p.Thr296Met

Likely Pathogenic

Autism Spectrum Disorder

N/R

N/R

N/R

N/R

-

Marcogliese (2022), cell Report 15;38 [37]

NM_002063.4(GLRA2):c.1334G > A

Missense

p.Arg445Gln

Likely Pathogenic

Not Provided

Yes

Yes

Yes

Yes

Seizure, Autistic Disorder, Cognitive Impairment, Short Attention Span, Sleep Disturbance, Downslanted Palpebral Fissures

ClinVar (RCV001813920.1)

NM_002063.4(GLRA2): c.1048C > T

Patient 1

Missense

p.Arg350Cys

Likely Pathogenic

Intellectual Developmental Disorder, X-Linked, Syndromic, Pilorge Type

Yes

Yes

Yes

Yes

Seizures, PDD, Some Facial Features such as; a Broad Face, Prominent Lips, Broad Eyebrows, Long Eyelashes, Prominent Eyelashes, and a Broad Nasal Tip. Normal EEG (in proband)

Current Study

Patient 2