Clinical and genetic characterization of a progressive RBL2-associated neurodevelopmental disorder.

Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants.

ELMO2-related intraosseous vascular malformation: new cases with novel pathogenic variants, clinical follow-up and therapeutic approaches.

Primary intraosseous vascular malformation (VMPI, #606893) is an ultra-rare disorder caused by biallelic pathogenic variants in ELMO2. To date, only six families with pathogenic ELMO2 variants causing a VMPI phenotype have been described. VMPI is characterized by vascular malformations that compress the facial bones, often leading to life-threatening complications, such as massive bleeding and intracranial herniation.

Exploring molecular spectrum in thai patients with maple syrup urine disease: unveiling a common variant.

Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by variants in any of the following genes: BCKDHA, BCKDHB, and DBT gene. Previous reports have highlighted a variety of common causing genes and variants among different ethnic groups affected by MSUD. This study is the first to describe the molecular characteristics, potential common variants, clinical phenotypes, and treatment outcomes of 20 Thai MSUD patients before the implementation of expanded newborn screening in Thailand.

46,ΧΥ DSD in an adolescent with a novel de novo variant of the NR5A1 gene - case report and literature review.

Purpose: In addition to chromosomal abnormalities, several genes have been implicated as causes of disorders of sex development (DSD). The NR5A1 gene expresses SF1, a transcription factor that plays a role in steroidogenesis by controlling multiple stages of adrenal and gonadal development, its mutations having been reported in cases of DSD.

Case Presentation: A 15-year-old teenager was admitted to the Children's ICU of a tertiary center due to acute encephalitis.

Deciphering the etiology of undiagnosed ocular anomalies along with systemic alterations in pediatric patients through whole exome sequencing.

Inherited and developmental eye diseases are quite diverse and numerous, and determining their genetic cause is challenging due to their high allelic and locus heterogeneity. New molecular approaches, such as whole exome sequencing (WES), have proven to be powerful molecular tools for addressing these cases. The present study used WES to identify the genetic etiology in ten unrelated Mexican pediatric patients with complex ocular anomalies and other systemic alterations of unknown etiology.

Clinical and molecular characteristics of Korean patients with Kabuki syndrome.

Introduction: Kabuki syndrome (KS) is a rare disorder characterized by typical facial features, skeletal anomalies, fetal fingertip pad persistence, postnatal growth retardation, and intellectual disabilities. Heterozygous variants of the KMT2D and KDM6A genes are major genetic causes of KS. This study aimed to report the clinical and genetic characteristics of KS.

Clinical and genetic characteristics of three patients with congenital insensitivity to pain with anhidrosis: Case reports and a review of the literature.

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss-of-function mutations of the NTRK1 gene, affecting the autonomic and sensory nervous system. Clinical manifestation is varied and includes recurrent fever, pain insensitivity, anhidrosis, self-mutilating behavior, and intellectual disability.

Methods: Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing.

Whole exome sequencing in Serbian patients with hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with a high genetic and clinical heterogeneity. Numerous HSP patients remain genetically undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel variants and genes is needed.

PKHD1L1, a gene involved in the stereocilia coat, causes autosomal recessive nonsyndromic hearing loss.

Identification of genes associated with nonsyndromic hearing loss is a crucial endeavor given the substantial number of individuals who remain without a diagnosis after even the most advanced genetic testing. PKHD1L1 was established as necessary for the formation of the cochlear hair-cell stereociliary coat and causes hearing loss in mice and zebrafish when mutated. We sought to determine if biallelic variants in PKHD1L1 also cause hearing loss in humans.

A case report of an Egyptian family with familial hypercholesterolemia and an exonic LINE-1 insertion in LDLR.

Background: Familial hypercholesterolemia (MIM: PS143890) is a genetic disorder characterized by an increase in blood cholesterol. LDLR is one of the genes which their defect contributes to the disorder. Affected individuals may carry a heterozygous variant or homozygous/compound heterozygous variants and those with biallelic pathogenic variants present more severe symptoms.

Familial focal segmental glomerulosclerosis associated with a WT1 gene missense mutation: A case report.

Focal s egmental glomerulosclerosis (F SGS) can cause protei nuria and loss o f k idney fun ction, leading to e ndstage renal di s ease (ESRD). Podocyte injury is the ce ntral pathophysiologi cal mechanis m of hereditary FSGS. Numerous mutations in genes e ncoding or affe cting the transcriptional regulation of podocyte cell compar tments have been detected in patients with genetic FSGS.

Progressive ataxia, ophthalmoparesis, and hypogonadotropic hypogonadism in a family with a novel variant in the KIFBP gene.

A novel homozygous variant in KIFBP was identified in a consanguineous family with four sibs affected by Goldberg-Sphrintzen Syndrome (GOSHS). We report for the first time, early-adulthood-onset progressive ataxia, opthalmoparesis, and hypogonadotropic hypogonadism in GOSHS.

, A Gene Involved in the Stereocilia Coat, Causes Autosomal Recessive Nonsyndromic Hearing Loss.

Identification of genes associated with nonsyndromic hearing loss is a crucial endeavor given the substantial number of individuals who remain without a diagnosis after even the most advanced genetic testing. was established as necessary for the formation of the cochlear hair-cell stereociliary coat and causes hearing loss in mice and zebrafish when mutated. We sought to determine if biallelic variants in also cause hearing loss in humans.

Clinical, radiographic and molecular characterization of two unrelated families with multicentric osteolysis, nodulosis, and arthropathy.

Background: Multicentric osteolysis nodulosis and arthropathy (MONA) is a rare autosomal recessive disorder characterized by marked progressive bone loss and joint destruction resulting in skeletal deformities. MONA is caused by MMP2 deficiency. Here we report clinical and molecular analyses of four patients in two families from Pakistan and Finland.

LONG-TERM CLINICAL OUTCOMES AND GENOTYPE-PHENOTYPE CORRELATION IN FAMILIAL EXUDATIVE VITREORETINOPATHY IN A TERTIARY REFERRAL CENTER.

Background/purpose: To evaluate clinical outcomes and assess genotype-phenotype correlations in patients with familial exudative vitreoretinopathy (FEVR).

Methods: Clinical charts of 40 patients with FEVR were reviewed. FEVR was staged per Pendergast and Trese, and retinal dragging and folds further classified per Yaguchi et al.

Maternal mosaicism in SSBP1 causing optic atrophy with retinal degeneration: implications for genetic counseling.

Background: Optic atrophy-13 with retinal and foveal abnormalities (OPA13) (MIM #165510) is a mitochondrial disease in which apparent bilateral optic atrophy is present and sometimes followed by retinal pigmentary changes or photoreceptors degeneration. OPA13 is caused by heterozygous mutation in the SSBP1 gene, associated with variable mitochondrial dysfunctions.

Results: We have previously reported a 16-year-old Taiwanese male diagnosed with OPA13 and SSBP1 variant c.

Combined immunodeficiency and impaired PI3K signaling in a patient with biallelic LCP2 variants.

Background: Inborn errors affecting components of the T-cell receptor signaling cascade cause combined immunodeficiency with various degrees of severity. Recently, homozygous variants in LCP2 were reported to cause pediatric onset of severe combined immunodeficiency with neutrophil, platelet, and T- and B-cell defects.

Objective: We sought to unravel the genetic cause of combined immunodeficiency and early-onset immune dysregulation in a 26-year-old man who presented with specific antibody deficiency, autoimmunity, and inflammatory bowel disease since early childhood.