This study identified a variant in ZCCHC8 in a family with pulmonary fibrosis, elevated liver enzymes and short telomeres and a novel variant in the J6a-6.1 region of TERC in a family with pulmonary fibrosis, hematological disease, and short telomeres. Abstract Telomere biology disorder (TBD) can present within a wide spectrum of symptoms ranging from severe congenital malformations to isolated organ dysfunction in adulthood. Diagnosing TBD can be challenging given the substantial variation in symptoms and age of onset across generations. In this report, we present two families, one with a p ..read more

This is the first report of a severe neurodevelopmental delay disorder attributed to a biallelic loss-of-function deletion in CTNND2. Other clinical features included microcephaly, short stature, lower limb hypertonia, and kyphosis. This clinical entity is distinct from the mild condition caused by monoallelic CTNND2 alterations, here named as Rauch-Azzarello syndrome. Abstract CTNND2 encodes δ-catenin, a component of an adherens junction complex, and plays an important role in neuronal structure and function. To date, only heterozygous loss-of-function CTNND2 variants have been associated w ..read more

We describe a cohort of 39 Chinese patients with glycogen storage diseases type I, VI, and IX. Thirty-two mutations in G6PC1, PYGL, PHKA2, and PHKB genes were identified, with 14 of them being novel variants. A deep phenotypic characterization of the cohort was also described. Abstract Glycogen storage diseases (GSDs) are abnormally inherited glycogen metabolism mainly affecting the liver, muscles, and heart. Deficiency of proteins involved in glycogen metabolism caused by genetic mutations are responsible for different subtype of GSDs. However, there are still some challenges in diagnosing ..read more

The cover image is based on the Short Report Feasibility of whole-exome sequencing in fine-needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations by Liyuan Ma et al., https://doi.org/10.1111/cge.14494. The cover image is based on the Short Report Feasibility of whole-exome sequencing in fine-needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations by Liyuan Ma et al., https://doi.org/10.1111/cge.14494 ..read more

Clinical Genetics, Volume 105, Issue 5, Page 457-457, May 2024 ..read more

Admixture refers to the mixing of genetic backgrounds within individuals in a population. Sometimes this mixture can be associated with a specific trait. We developed a fast machine learning tool called Admix-AI that uses genetic ancestry informative DNA markers to determine the amount of admixed DNA so that genetically similar individuals can be sorted into genetically similar groups to improve the detection of the genetic underpinnings of a trait. Abstract Admixture refers to the mixing of genetic ancestry from different populations. Admixture is important for genomic medicine because it c ..read more

After assembling a French cohort of 15 families with 40 carriers of the Xq28 int22h-1/int22h-2 duplication, we found that the penetrance of the associated syndromic intellectual disability was less than 100% in our male individuals and less than 50% in our female individuals, inconsistent with previous descriptions in the literature. Abstract Xq28 int22h-1/int22h-2 duplication is the result of non-allelic homologous recombination between int22h-1/int22h-2 repeats separated by 0.5 Mb. It is responsible for a syndromic form of intellectual disability (ID), with recurrent infections and atopic ..read more

Putative phenotypic impact of FOXL2 variants. The different sub-units of the preproprotein are indicated: the peptide signal (gray); the poly-glycine region (green); the Forkhead region (yellow); the two conserved poly-alanine regions (red) and the poly-proline region (dark blue). The three phenotypes are indicated: Blepharophimosis, ptosis, and epicanthus inversus syndrome with primary ovarian failure type I (BPES-I), Blepharophimosis, ptosis, and epicanthus inversus syndrome with no primary ovarian failure type II (BPES-II), and Primary ovarian failure (POI). Black asterisks indicated the l ..read more

A total of 25 patients <20 years with biallelic KIF12 variants reviewed. Presentation with elevated serum transaminase and gamma-glutamyl transpeptidase activity.Liver transplantation in 7 cases. Genotype–phenotype correlation not apparent. KIF12 is incompletely annotated in GRCh37. Abstract Exome sequencing (ES) has identified biallelic kinesin family member 12 (KIF12) mutations as underlying neonatal cholestatic liver disease. We collected information on onset and progression of this entity. Among consecutively referred pediatric patients at our centers, diagnostic ES identified 4 patie ..read more

This study presents clinical and molecular data for 24 neonates with perinatal hypoxic–ischemic encephalopathy who underwent exome or genome sequencing. 25% of neonates undergoing sequencing received a genetic diagnosis, and another 25% had suggestive but indeterminate genetic results. Diagnoses occurred in cases with and without compelling evidence of perinatal hypoxia. Abstract Hypoxic–ischemic encephalopathy (HIE) occurs in up to 7 out of 1000 births and accounts for almost a quarter of neonatal deaths worldwide. Despite the name, many newborns with HIE have little evidence of perinatal h ..read more