Molecular and Functional Characterisation of a Novel Intragenic 12q24.21 Deletion Resulting in Haploinsufficiency Syndrome.

Heterozygous pathogenic variants in the gene cause impaired intellectual development and distinctive facial features with or without cardiac defects (MIM #616789). This complex neurodevelopmental disorder is characterised by various phenotypic features, including plagiocephaly, strabismus, clubfoot, poor speech, and developmental delay. The aim of this study was to evaluate the clinical significance and consequences of a novel heterozygous intragenic deletion in a proband with clinical features of a -related disorder through extensive clinical, molecular, and functional characterisation.

PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation.

Background and Objectives: Pathogenic variants of PIGN are a known cause of multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). Many affected individuals have clinical features overlapping with Fryns syndrome and are mainly characterised by developmental delay, congenital anomalies, hypotonia, seizures, and specific minor facial anomalies. This study investigates the clinical and molecular data of three individuals from two unrelated families, the clinical features of which were consistent with a diagnosis of MCAHS1.

Donor Splice Site Variant in Causes Christianson Syndrome in a Lithuanian Family: A Case Report.

Background and Objectives: The pathogenic variants of SLC9A6 are a known cause of a rare, X-linked neurological disorder called Christianson syndrome (CS). The main characteristics of CS are developmental delay, intellectual disability, and neurological findings. This study investigated the genetic basis and explored the molecular changes that led to CS in two male siblings presenting with intellectual disability, epilepsy, behavioural problems, gastrointestinal dysfunction, poor height, and weight gain.

A de novo 13q31.3 microduplication encompassing the miR-17 ~ 92 cluster results in features mirroring those associated with Feingold syndrome 2.

Hemizygosity of the MIR17HG gene encoding the miR-17 ~ 92 cluster is associated with Feingold syndrome 2 characterized by intellectual disability, skeletal abnormalities, short stature, and microcephaly. Here, we report on a female with a de novo 13q31.3 microduplication encompassing MIR17HG but excluding GPC5.

A case report of familial 4q13.3 microdeletion in three individuals with syndromic intellectual disability.

Background: Interstitial 4q deletions are rare chromosomal alterations. Most of the previously reported deletions involving the 4q13.3 region are large chromosomal alterations with a common loss of band 4q21 resulting in marked growth restriction, severe intellectual disability, and absent or severely delayed speech.

Novel GLI3 variant causes Greig cephalopolysyndactyly syndrome in three generations of a Lithuanian family.

Background: Preaxial polydactyly type IV, also referred as polysyndactyly, has been described in a few syndromes. We present three generations of a family with preaxial polydactyly type IV and other clinical features of Greig cephalopolysyndactyly syndrome (GCPS).

Methods And Results: Sequencing analysis of the GLI3 coding region identified a novel donor splice site variant NC_000007.

A novel CHD7 variant disrupting acceptor splice site in a patient with mild features of CHARGE syndrome: a case report.

Background: CHARGE syndrome (MIM# 214800)-which is characterised by a number of congenital anomalies including coloboma, ear anomalies, deafness, facial anomalies, heart defects, atresia choanae, genital hypoplasia, growth retardation, and developmental delay-is caused by a heterozygous variant in the CHD7 (MIM# 608892) gene located on chromosome 8q12. We report the identification of a novel c.5535-1G > A variant in CHD7 and provide the evaluation of its effect on pre-mRNA splicing.

A de novo Pericentric Inversion in Chromosome 4 Associated with Disruption of PITX2 and a Microdeletion in 4p15.2 in a Patient with Axenfeld-Rieger Syndrome and Developmental Delay.

Axenfeld-Rieger syndrome (ARS) is a clinically and genetically heterogeneous group of autosomal dominantly inherited malformations that predominantly affect the eye but are also associated with craniofacial dysmorphism and dental abnormalities. A broad spectrum of genetic alterations involving PITX2 and FOXC1 lead to ARS. We report on a 4-year-old girl with clinical features of ARS and developmental delay due to a de novo apparently balanced pericentric inversion in chromosome 4.

Features of KAT6B-related disorders in a patient with 10q22.1q22.3 deletion.

Background: Blepharophimosis is a fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures. It is a rare facial malformation and is considered an important diagnostic feature in dysmorphic analysis. It is likely that many patients with blepharophimosis-mental retardation syndrome have submicroscopic chromosomal rearrangements, and the use of molecular karyotyping can narrow the known blepharophimosis-mental retardation-critical regions or clarify the effect of the haploinsufficiency of the involved genes on the phenotype.

Identification of genetic causes of congenital neurodevelopmental disorders using genome wide molecular technologies.

Background: Intellectual disability affects about 1-2% of the general population worldwide, and this is the leading socio-economic problem of health care. The evaluation of the genetic causes of intellectual disability is challenging because these conditions are genetically heterogeneous with many different genetic alterations resulting in clinically indistinguishable phenotypes. Genome wide molecular technologies are effective in a research setting for establishing the new genetic basis of a disease.