Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders.

The pre-mRNA-processing factor 8, encoded by PRPF8, is a scaffolding component of a spliceosome complex involved in the removal of introns from mRNA precursors. Previously, heterozygous pathogenic variants in PRPF8 have been associated with autosomal dominant retinitis pigmentosa. More recently, PRPF8 was suggested as a candidate gene for autism spectrum disorder due to the enrichment of sequence variants in this gene in individuals with neurodevelopmental disorders.

Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues.

X-linked myotubular myopathy (XLMTM), a severe congenital myopathy, is caused by mutations in the MTM1 gene located on the X chromosome. A majority of affected males die in the early postnatal period, whereas female carriers are believed to be usually asymptomatic. Nevertheless, several affected females have been reported.

Widening the spectrum of filamin-C myopathy: Predominantly proximal myopathy due to the p.A193T mutation in the actin-binding domain of FLNC.

We report three patients with a predominantly proximal myopathy due to p.A193T mutation in the actin-binding domain of FLNC, which has so far only been associated with a distal myopathy. They presented with a late onset myopathy characterized by predominant limb-girdle and proximal weakness.

Refining the Diagnosis of Congenital Nephrotic Syndrome on Long-term Stored Tissue: c.1097G>A (p.(Arg366His)) WT1 Mutation Causing Denys Drash Syndrome.

Congenital nephrotic syndrome (CNS) caused by a mutation in the Wilms tumor 1 suppressor gene (WT1) is part of Denys Drash Syndrome or Frasier syndrome. In the framework of genetic counseling, the diagnosis of CNS can be refined with gene mutation studies on long-term stored formalin-fixed paraffin-embedded tissue from postmortem examination. We report a case of diffuse mesangial sclerosis with perinatal death caused by a de novo mutation in the WT1 gene in a girl with an XY-genotype.

Bartter syndrome type III and congenital anomalies of the kidney and urinary tract: an antenatal presentation.

Bartter syndrome encompasses a variety of inheritable renal tubular transport disorders characterized by hypokalemia and hypochloremic metabolic alkalosis. Bartter syndrome Type III is caused by genetic alterations in the chloride channel kidney B (CLCNKB) gene and often presents in the first 2 years of life, known as classic Bartter syndrome. However, in rare cases Bartter syndrome Type III has an antenatal presentation with polyhydramnios, premature delivery and severe dehydration in the first weeks of life.

Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome.

Gitelman syndrome (GS) is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis in conjunction with significant hypomagnesemia and hypocalciuria. The GS phenotype is caused by mutations in the solute carrier family 12, member 3 (SLC12A3) gene that encodes the thiazide-sensitive NaCl cotransporter (NCC). We analyzed DNA samples of 163 patients with a clinical suspicion of GS by direct sequencing of all 26 exons of the SLC12A3 gene.

Clinical presentation and the presence of hearing impairment in branchio-oculo-facial syndrome: a new mutation in the TFAP2A gene.

We report on the clinical presentation of branchio-oculo-facial (BOF) syndrome in 2 patients with mutations in the TFAP2A gene (OMIM 107580). This TFAP2A gene was recently shown to be involved in the causation of BOF syndrome. An overview of the literature on BOF syndrome is given based on clinical reports written in the period during which mutation analysis was not yet available for BOF syndrome.