Similarity of Phenotype in Three Male Patients With the c.320A>G Variant in ALG13: Possible Genotype-Phenotype Correlation.

Background: Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG-1 syndromes, most of which are inherited as autosomal recessive traits, although X-linked inheritance has also been reported. Pathogenic variants in the asparagine-linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36).

Germline mosaicism in a family with haploinsufficiency.

Haploinsufficiency of the methyl-CpG-binding domain protein 5 () gene causes a neurodevelopmental disorder that includes intellectual disability, developmental delay, speech impairment, seizures, sleep disturbances, and behavioral difficulties. Microdeletion of 2q23.1 is the most common cause of haploinsufficiency, although haploinsufficiency may also cause this genetic disorder.

De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy.

X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L- and M- cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay.

De Novo interstitial deletion 13q33.3q34 in a male patient with double outlet right ventricle, microcephaly, dysmorphic craniofacial findings, and motor and developmental delay.

We describe a 6-year-old male, diagnosed at birth with double outlet right ventricle (DORV), anterior aorta, multiple ventricular septal defects, pulmonary stenosis, microcephaly and mildly dysmorphic craniofacial findings. Chromosomal analysis showed a normal male karyotype but on subsequent array comparative genomic hybridization (array CGH) analysis a de novo 2.5 Mb loss in chromosome 13q at 13q33.

De novo interstitial deletion 2q14.1q22.1: is there a recognizable phenotype?

In this report we describe a male patient with a rare de novo interstitial deletion of chromosome 2q14.1-q22.1.

TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function.

Topoisomerase II (TOP2) removes torsional stress from DNA and facilitates gene transcription by introducing transient DNA double-strand breaks (DSBs). Such DSBs are normally rejoined by TOP2 but on occasion can become abortive and remain unsealed. Here we identify homozygous mutations in the TDP2 gene encoding tyrosyl DNA phosphodiesterase-2, an enzyme that repairs 'abortive' TOP2-induced DSBs, in individuals with intellectual disability, seizures and ataxia.

Autosomal recessive cutis laxa type 2A (ARCL2A) mimicking Ehlers-Danlos syndrome by its dermatological manifestations: report of three affected patients.

Through a survey of more than 20 patients with a specific subgroup of autosomal recessive congenital cutis laxa (ARCL), namely ATP6V0A2-related cutis laxa, we noted that the clinical findings on three patients included pretibial pseudo-ecchymotic skin lesions very similar to those found in classical Ehlers-Danlos syndrome. The finding is apparently age-related, occurring during the second decade in two of the three patients.

Chromosome 22q11.21 microduplication in association with hypoplastic left heart syndrome with hypoplastic pulmonary arteries.

We describe a case of a baby girl born with hypoplastic left heart syndrome consisting of mitral atresia, aortic atresia, hypoplastic ascending aorta, and left ventricle. The pulmonary arteries were hypoplastic, measuring 3 mm. Fluorescence in situ hybridisation analysis demonstrated a microduplication of chromosome 22q11.

Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing.

Background: Intellectual disability (ID) is a common neurodevelopmental disorder affecting 1-3% of the general population. Mutations in more than 10% of all human genes are considered to be involved in this disorder, although the majority of these genes are still unknown.

Objectives: We investigated 19 small non-consanguineous families with two to five affected siblings in order to identify pathogenic gene variants in known, novel and potential ID candidate genes.

Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis.

Desbuquois dysplasia (DD) is characterized by antenatal and postnatal short stature, multiple dislocations, and advanced carpal ossification. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. We have identified mutations in calcium activated nucleotidase 1 gene (CANT1) in DD type 1.

Loss-of-function mutations in ATP6V0A2 impair vesicular trafficking, tropoelastin secretion and cell survival.

Autosomal recessive cutis laxa type 2 (ARCL2), a syndrome of growth and developmental delay and redundant, inelastic skin, is caused by mutations in the a2 subunit of the vesicular ATPase H+-pump (ATP6V0A2). The goal of this study was to define the disease mechanisms that lead to connective tissue lesions in ARCL2. In a new cohort of 17 patients, DNA sequencing of ATP6V0A2 detected either homozygous or compound heterozygous mutations.

Mutations in the embryonal subunit of the acetylcholine receptor (CHRNG) cause lethal and Escobar variants of multiple pterygium syndrome.

Multiple pterygium syndromes (MPSs) comprise a group of multiple-congenital-anomaly disorders characterized by webbing (pterygia) of the neck, elbows, and/or knees and joint contractures (arthrogryposis). In addition, a variety of developmental defects (e.g.