Mitochondrial Complex V Deficiency Caused by a Homozygous Splice Variant in ATP5PO.

Most complex V subunits are nuclear encoded and so far, were not found in association with recognized Mendelian disorders. ATP5PO is a candidate gene for complex V mitochondrial disease. It encodes the oligomycin sensitivity-conferring protein (OSCP), an essential component of the "stalk" region that links the F1 and F0 domains of the ATP synthase complex.

Atypical presentation of anorexia nervosa pediatric patient: A multidisciplinary approach to diagnosis and management.

This case report describes the complex presentation, diagnostic problems, and multidisciplinary therapy of a 13-year-old Syrian girl with an unusual form of anorexia nervosa (AN). The goal is to improve understanding of AN's varied clinical spectrum while emphasizing the significance of a complete diagnostic approach and multidisciplinary therapy in juvenile cases. The patient reported considerable weight loss, amenorrhea, and physical indications of starvation over the previous two months.

Genetics of Primary Adrenal Insufficiency Beyond CAH in Saudi Arabian Population.

Background: The use of exome sequencing (ES) has helped in detecting many variants and genes that cause primary adrenal insufficiency (PAI). The diagnosis of PAI is difficult and can be life-threatening if not treated urgently. Consanguinity can impact the detection of recessively inherited genes.

Further delineation of the SCAF4-associated neurodevelopmental disorder.

While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder.

Parkinsonism-dystonia-2: Case-series study from Saudi Arabia.

Parkinsonism-dystonia-2 PKDYS2 is an autosomal-recessive disorder, caused by pathogenic biallelic variants in SLC18A2 which encodes the vesicular monoamine transporter (VMAT2) protein. PKDYS2 is a treatable neurotransmitter disease, and the rate of diagnosis of this disorder has increased significantly with the advance of genomic technologies. Our report highlights a novel pathologic variant in one case and a novel finding on MRI Brain, consisting of a normal symmetrical signal intensity in the dorsal brainstem and pons, and it substantiates the significance of genetic testing in the evaluation of children with developmental delays, which influences clinical decisions to enhance patient outcomes.

Vitamin D-binding protein deficiency: an underrecognized Mendelian disorder of vitamin D metabolism.

Vitamin D-binding protein (VDBP) deficiency is a recently discovered apparently benign biochemical disorder that can masquerade as treatment-resistant vitamin D deficiency and is likely underrecognized. We present the case of a child with persistently low 25OH vitamin D levels despite replacement therapy. Exome sequencing revealed a novel homozygous nonsense variant in the GC gene, leading to undetectable levels of VDBP.

A molecular study of pediatric pilomyxoid and pilocytic astrocytomas: Genome-wide copy number screening, retrospective analysis of clinicopathological features and long-term clinical outcome.

Background: Pilocytic Astrocytoma (PA) is the most common pediatric brain tumors. PAs are slow-growing tumors with high survival rates. However, a distinct subgroup of tumors defined as pilomyxoid astrocytoma (PMA) presents unique histological characteristics and have more aggressive clinical course.

Gonadal mosaicism in GNAO1 causing neurodevelopmental disorder with involuntary movements; two additional variants.

Background: encodes an alpha subunit of the heterotrimeric guanine nucleotide-binding proteins (G proteins). Mutations in result in two clinical phenotypes: Early infantile epileptic encephalopathy 17 (EEIE17-OMIM #615473) and Neurodevelopmental disorder with involuntary movements (NEDIM-OMIM #617493). Both are inherited as autosomal dominant disorders and originate mainly as de novo.

SLC25A42-associated mitochondrial encephalomyopathy: Report of additional founder cases and functional characterization of a novel deletion.

SLC25A42 is the main transporter of coenzyme A (CoA) into mitochondria. To date, 15 individuals have been reported to have one of two bi-allelic homozygous missense variants in the as the cause of mitochondrial encephalomyopathy, of which 14 of them were of Saudi origin and share the same founder variant, c.871A > G:p.

Further delineation of van den Ende-Gupta syndrome: Genetic heterogeneity and overlap with congenital heart defects and skeletal malformations syndrome.

Van den Ende-Gupta syndrome (VDEGS) is a rare autosomal recessive condition characterized by distinctive facial and skeletal features, and in most affected persons, by biallelic pathogenic variants in SCARF2. We review the type and frequency of the clinical features in 36 reported individuals with features of VDEGS, 15 (42%) of whom had known pathogenic variants in SCARF2, 6 (16%) with negative SCARF2 testing, and 15 (42%) not tested. We also report three new individuals with pathogenic variants in SCARF2 and clinical features of VDEGS.