In skeletal health, the importance of other transcriptional products encoded by GNAS genes (e.g., XLαs, extralarge variant of Gsα), in addition to the α-subunit of the activating heterotrimeric G protein (Gsα), cannot be ignored. Abnormal expression of Gsα is associated with certain tumors and Osteofibrous dysplasia (OFD)/McCune-Albright syndrome (activating mutations), pseudohypoparathyroidism(PHP) and related diseases (inactivating mutations). In our review, we found that deletion of XLαs expression can synergize with Gsα to participate in the development of progressive osseous heteroplasia (POH) in PHP-related diseases by regulating the cAMP-PKA signaling pathway, affect bone remodeling through the Phospholipase C β4-inositol triphosphate-Ca²⁺ pathway and may even act as an inhibitor of clathrin-induced endocytosis in osteocytes.

We found selective pattern between failure of tooth eruption and causative mutated genes. We recommend selective failure of tooth eruption (SFTE) to classify those genetic unerupted teeth which showed higher incidence of eruption failure in specific tooth, with or without other dental anomalies.

• Among 172 pediatric or adult patients with various kidney diseases, WES diagnosed genetic kidney diseases in 63 (36.6%) patients.
• Higher diagnostic yield was detected in younger age at onset or in tubulo-interstitial disease phenotype.
• Renal phenotypes (16%) reclassified and management (16%) changed after the genetic diagnosis.

Mutation of rs112872667 in ICAM-1 genehave critical predictive value on the prognosis of ICM, ICM patients with themutant genotype (CT or TT) have good prognosis than those withthe wild genotype (CC).

• A homozygous founder variant in PDE2A leads to paroxysmal dyskinesia in three Pakistani families.
• Patient fibroblasts revealed aberrant mitochondrial morphology compared to the controls.
• The identified variant is predicted to result in an empty space in the core of the protein leading to instability of the protein.

The proposed screening apprach resulted in the predictive identification of at risk individuals in our population cohort with a positive predictive value of 90%. For the clinically diagnosed hypercholesterolemia patients, a more precise diagnosis of the underlying disease etiology is provided by analysing monogenic causes and gentic risk scores associated with increased LDL-C and particularly Lp(a). We found nine novel variants in FH genes and increaded diagnostic yield from 46.6% to 68.8% allowing individualized treatment strategies in the future.

Elbendary et al. report a new Egyptian patient with alopecia-intellectual disability syndrome type 4 (APMR4) and cerebellar involvement due to novel compound heterozygous LSS splice site (c.14+2T>C) and missense (c.1357 G>A; p.V4531) variants. A review of all reported variants to date in 29 families with LSS-related phenotypes showed an emerging genotype–phenotype correlation.

PRNP octapeptide repeat alteration mutations are present in sporadic AD and FTD patients. One late-onset FTD patient and one early-onset AD patient each had a 2-OPRD in PRNP, while one early-onset AD patient had a PRNP 5-OPRI mutation.

A homozygous founder variant in PPIL1 gene leads to a recognizable type of pontocerebellar hypoplasia associated with developmental brain malformation and congenital severe microcephaly.

We performed cDNA sequencing of CACNA1A in 11 patients with episodic ataxia or congenital ataxia in whom a variant of unknown significance predicted to modify splicing was identified. This analyze was done on RNA obtained from fibroblastic cell lines and allowed the classification of the variants.

Biallelic pathogenic variants in the NAA20 gene have been described in 7 individuals belonging to 3 separate families. These variants functionally results in a reduced cellular N-acetylation, leading to a phenotypic spectrum that includes developmental delay, cognitive impairment, microcephaly, ataxia, epilepsy, brain malformations, congenital heart defects, and craniofacial dysmorphisms.

Whole genome sequencing (WGS) data, produced from clinically ordered panels built as bioinformatic slices for 16 clinically diverse, undiagnosed cases, were reanalyzed using a machine-learning-based tool for variant prioritization and yielded additional potentially clinically significant variants in five out of 16 cases including a complex variant not detectable by exome.

Interestingly, disease-causing mutations in the ANK2 gene have been identified in patients with autism since 2012, though with no full clinical description. In this Research Letter, for the first time, we describe the detailed characteristics of a patient with autism caused by a new mutation in this gene. Our report is a first step to better understanding ANK2-related autism and will contribute to facilitating its further diagnosis.

We identified a novel compound heterozygous RBCK1 mutation including a synonymous pathogenic variant in the last codon of sixth exon in an adult-onset patient with mild presentations, which extends the genotypic and phenotypic spectra of PGBM1.

We describe a patient from the 100,000 Genomes Project with a complex de novo structural variant within KMT2E leading to O'Donnell-Luria-Rodan syndrome. This case expands the mutational spectrum for this syndrome and highlights the importance of revisiting unsolved cases using better SV prioritisation tools and updated gene panels.

Pigmentary abnormalities in Coffin-Siris Syndrome should be considered as part of the wide phenotypical spectrum of this patients.