A Report of a Child with SEC31A-Related Neurodevelopmental Disorder
Abstract
:1. Introduction
2. Results
2.1. Case Report
2.2. The Variant and in Silico Pathogenesis Analysis
2.3. Gene Network Analysis (GNA)
2.4. Structural Modeling of the Variant
2.5. ACMG Classification of c.1359C > G; p.Cys453Trp
3. Discussion
4. Materials and Methods
4.1. DNA Isolation, Polymerase Chain Reaction (PCR)
4.2. Whole Exome Sequencing (WES)
4.3. Whole Genome Sequencing (WGS)
4.4. Confirmatory Sanger Sequencing
4.5. Computational Structural Analysis of Mutants
4.6. Gene Network Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Prediction Tool | Score/Result | Pathogenicity Threshold | Interpretation * | Reference |
---|---|---|---|---|
AlphaMissense | 0.9915 | >0.564 | Pathogenic (top 5% of pathogenic variants, rankscore = 0.95066) | [14] |
BayesDel_addAF | 0.3517 | >0.16 = Pathogenic | Pathogenic (supports deleteriousness) | [15] |
BayesDel_noAF | 0.2674 (D) | >0.16 = Pathogenic | Pathogenic (independent of allele frequency) | [15] |
CADD | 21.6 | >20 | Pathogenic (top 1% of deleterious variants genome-wide) | [16] |
ClinPred | 0.9998 | >0.5 = Pathogenic | Pathogenic (near-maximal confidence) | [12] |
DANN | 0.992 | >0.95 | Pathogenic (high-confidence prediction) | [17] |
DEOGEN2 | 0.65427 | 0.89546 | Deleterious prediction | [18] |
ESM1b/Variped | −18.109 | Lower = Deleterious | Deleterious (rankscore = 0.9965, “D” prediction) | [19] |
Fathmm MKL | 0.9551 | >0.5 = Deleterious | Deleterious (group AEFGBI: likely functional impact) | [20] |
Fathmm XF | 0.8938 | >0.5 = Deleterious | Deleterious (high confidence) | [21] |
LRT | 0 | <0.05 = Deleterious | Deleterious (low conservation tolerance) | [22] |
M_CAP | 0.1809 | >0.025 = Pathogenic | Pathogenic (moderate support) | [23] |
MetaRNN | 0.9436 | >0.5 = Pathogenic | Pathogenic (high confidence) | [13] |
MutPred | 0.767 | >0.5 | Pathogenic (rankscore = 0.89452; gain of MoRF binding, p = 0.0355) | [24] |
MutationTaster | 1.0 | N/A (qualitative) | Disease-Causing (simple_aae model) | [9] |
MutationAssessor | 3.575 | >3.5 = High Impact | High Impact (functional hotspot) | [25] |
Polyphen2 HDIV | 1.0 | >0.85 = Probably Damaging | Damaging (maximal confidence) | [8] |
Polyphen2 HVAR | 1.0 | >0.85 = Probably Damaging | Damaging (consistent with HDIV) | [8] |
PROVEAN | −10.38 | ≤−2.5 = Deleterious | Deleterious (far below threshold) | [26] |
REVEL | 0.498 | >0.5 | Uncertain significance (at border) | [27] |
SIFT | 0 | <0.05 = Deleterious | Deleterious (strong evolutionary disruption) | [28] |
SIFT4G | 0 | <0.05 = Deleterious | Deleterious (matches SIFT’s prediction) | [29] |
This Study | Almontashiri et al. (2024) [6] | Halperin et al. (2019) [4] | |||
---|---|---|---|---|---|
Family | 1 | 1 | 1 | 1 | |
Subjects | 1 | 1 | 1 | 2 | |
Gender | Male | Female | Female | Male | |
Age at presentation | 12 months | Antenatally | Birth | Birth | |
Age/outcome | 5 years (alive) | 15 days (died) | 4 years (died) | 2 years (died) | |
Consanguinity | (+) | (+) | (+) | (+) | |
Ethnicity | Arab | Arab | Middle east Bedouin | ||
Variant | c.DNA change | c.1359C > G | c.1435−1G > A | c.2776_2777 TA duplication | |
Amino acid change | p.Cys453Trp | - | p.A927fs*61 | ||
Zygosity | Homozygous | Homozygous | Homozygous | ||
Neurological findings | Seizures (generalized tonic–clonic) | No seizure | Seizures (focal and generalized tonic–clonic) | ||
Global developmental delay (cognition, motor, speech) Central hypotonia Hyperreflexia Spasticity | Hypotonia Hyperreflexia | Global developmental delay (cognition, motor, speech) Spastcic quadriplasia Hypotonia | |||
Neuroimaging | Corpus callosum hypogenesis Hypomyelination Diffuse brain atrophy | Interhemispheric cyst Absent corpus callosum | Semilobar holoprosencephaly Enlargement of the subarachnoid space Corpus callosum agenesis Ventriculomegaly Colpocephaly | ||
EEG | Abnormal electric activity | - | Disorganized background activity with an epileptic pattern of bilateral sharp waves and spikes discharges | ||
Growth parameters | Microcephaly Short stature | Microcephaly Short stature | Microcephaly | ||
Cardiac | Normal | Bradycardia | Peri-membranotic VSD | ||
Genitourinary | Normal | Normal | Normal | ||
GI problems | Constipation Dysphagia Recurrent aspiration Failure to thrive | Not reported | Pseudobulbar palsy Recurrent aspirations Congenital diaphragmatic hernia Umbilical and inguinal hernia Gastro-esophageal reflux Feeding difficulties Failure to thrive | ||
Ophthalmological | Esotropia | Not reported | Nystagmus Lack of ocular fixation Bilateral nuclear cataracts | ||
Dysmorphic features | Prominent nasal bridge, hypertelorism, epicanthal fold, frontal bossing, prominent ears | Wide anterior fontanelle, sloping forehead, hypertelorism, malformed ears, depressed nasal bridge, retrognathia, short neck Skeletal anomalies | Pointed triangular face, micrognathia and high-arched palate, thick lips, long eyelashes | ||
Hearing | Bilateral hearing loss | Not reported | Bilateral hearing loss |
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Share and Cite
AlTassan, R.; AlQudairy, H.; Saydo, B.; Alammari, A.; Londoño, K.J.C.; Ramzan, K.; Colak, D.; Arold, S.T.; Kaya, N. A Report of a Child with SEC31A-Related Neurodevelopmental Disorder. Int. J. Mol. Sci. 2025, 26, 5296. https://doi.org/10.3390/ijms26115296
AlTassan R, AlQudairy H, Saydo B, Alammari A, Londoño KJC, Ramzan K, Colak D, Arold ST, Kaya N. A Report of a Child with SEC31A-Related Neurodevelopmental Disorder. International Journal of Molecular Sciences. 2025; 26(11):5296. https://doi.org/10.3390/ijms26115296
Chicago/Turabian StyleAlTassan, Ruqaiah, Hanan AlQudairy, Biam Saydo, Aseel Alammari, Kelly J. Cardona Londoño, Khushnooda Ramzan, Dilek Colak, Stefan T. Arold, and Namik Kaya. 2025. "A Report of a Child with SEC31A-Related Neurodevelopmental Disorder" International Journal of Molecular Sciences 26, no. 11: 5296. https://doi.org/10.3390/ijms26115296
APA StyleAlTassan, R., AlQudairy, H., Saydo, B., Alammari, A., Londoño, K. J. C., Ramzan, K., Colak, D., Arold, S. T., & Kaya, N. (2025). A Report of a Child with SEC31A-Related Neurodevelopmental Disorder. International Journal of Molecular Sciences, 26(11), 5296. https://doi.org/10.3390/ijms26115296