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Advanced Neurology Genetics of neurodevelopmental disorders in Mexico

(Illumina, Inc., USA), which ensured that all targeted the Ethics Committee of the Hospital “Country 2000,” and
regions were sequenced with a minimum depth of 50×. all procedures were conducted following the standards of
The sequencing reads were then aligned to the reference the Declaration of Helsinki. Written and verbal informed
sequence GRCh37, which includes both intronic and consent was obtained from each participant (for adults) or
exonic regions, and copy number variants were determined. the parents (for children). All the cases and families were
All variants were reported in accordance with the Human numbered by order of inclusion.
Genome Variation Society guidelines. Confirmation of the
presence and location of reportable variants was performed 3. Results
as needed, based on stringent criteria, using one of several Twenty-four pediatric patients and 30 relatives from
validated orthogonal approaches. The results were,
13
further, analyzed by consulting databases such as PubMed, 11 families were included in our study. A diagnosis
GeneReviews, GNomad, ClinVar, and OMIM to correlate of Mendelian inheritance diseases was established in
clinical data with molecular findings. In cases involving 14 patients. However, 2 patients (patients 1 and 5)
variants of uncertain significance (VUS), a thorough were speculated with having genomic disorders due to
review was conducted using the Franklin tool by Genoox. aberrant results in copy number variants, which had
not yet been confirmed. In addition, eight VUSs with
2.3. Study design clinical and algorithmic relevance were identified. Only
This paper describes a descriptive observational study three out of the 24 patients did not receive a diagnosis
of a clinical series; therefore, we decided to present the or suspected diagnosis through the NGS study. The most
results individually with the specific data per patient so common clinical presentation among our patients was
that they can be adapted for a personalized-based clinical communication disorder, noted in 18 patients followed by
approach (Table 1). The study protocol was approved by ASD in 11 cases (Table 1).

Table 1. Clinical diagnoses, dysmorphia and/or functional disability, and molecular diagnoses per patient

No. Gender Age of Epilepsy ASD ADHD CD MD ID Dysmorphism Dysfunction Definitive diagnosis Familial
onset (Gene) study
1 θ M 3 months X X X Facial Generalized epilepsy Angelman syndrome. -
dysmorphism and Autoagresion Possible UPD 15q
limb defects genomic disorder
2 θ M 1 year X X X Facial Generalized epilepsy Developmental 2 Parents
dysmorphism impulsiveness encephalopathy 1 Sister
synaptopathy
(SYNGAP1)
3 θ F 2 months X Facial Suction and Developmental 2 Parents
dysmorphism swallowing encephalopathy 2 Siblings
impairment (CDKL5)
4 θ M At birth X X X Facial Poor suction Crisponi syndrome/ 2 Parents
dysmorphism, and swallowing cold-induced
scoliosis, and impairment sweating syndrome
camptodactyly (CRLF1)
Possible
channelopathy
(HCN1)
5 θ M At birth X X X Facial/limb defects Overgrowth Rule out Phelan– -
McDermid syndrome
(del22q13.2)
6 θ M 6 months X X Facial Pelvic girdle Danon disease -
dysmorphism dysfunction (LAMP2)
7 θ F At birth X X X Microcephaly Visual impairment Oxidative 2 Parents
and deafness phosphorylation
disorder 13 (PNPT1)
(Cont’d...)

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