A novel mutation in the gene associated with a new clinical finding: large brainstem.

We report the case of a Caucasian Spanish boy, who showed profound neonatal hypotonia, feeding difficulties, apnea, severe developmental delay, epilepsy, bilateral convergent strabismus, poor verbal language development and a large brainstem. Whole-exome sequence uncovered a novel mutation in the purine-rich element binding protein A gene (; NM_005859.4:c.

A novel de novo MTOR gain-of-function variant in a patient with Smith-Kingsmore syndrome and Antiphospholipid syndrome.

We report the clinical, biochemical and genetic findings from a Spanish girl of Caucasian origin who presented with macrocephaly, dysmorphic facial features, developmental delay, hypotonia, combined oxidative phosphorylation (OxPhos) deficiency, epilepsy and anti-phospholipid antibodies (aPL). Whole-exome sequencing (WES) uncovered a heterozygous variant in the MTOR gene (NM_004958.3: c.

A rare male patient with Fontaine progeroid syndrome caused by p.R217H de novo mutation in SLC25A24.

We report the clinical and genetic findings in a 15-year-old Spanish boy presenting prenatal and postnatal growth retardation, reduced subcutaneous adipose tissue, premature skin wrinkling, sparse hair, short distal phalanges with small nails, umbilical hernia, wide anterior fontanel, and normal cognitive and motor development. Exome sequencing uncovered a heterozygous mutation in SLC25A24 (NM_013386: c.650G>A: p.

Mitochondrial involvement in a Bosch-Boonstra-Schaaf optic atrophy syndrome patient with a novel de novo NR2F1 gene mutation.

We report the clinical and biochemical findings from a patient who presented with Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), an autosomal-dominant disorder characterized by optic atrophy, developmental delay and intellectual disability. In addition, the patient also displays hypotonia, stroke-like episodes, and complex IV deficiency of the mitochondrial respiratory chain. Whole-exome sequencing (WES) uncovered a novel heterozygous mutation in the NR2F1 gene (NM_005654:c.

An innovative strategy to clone positive modifier genes of defects caused by mtDNA mutations: MRPS18C as suppressor gene of m.3946G>A mutation in MT-ND1 gene.

We have developed a new functional complementation approach to clone modifier genes which overexpression is able to suppress the biochemical defects caused by mtDNA mutations (suppressor genes). This strategy consists in transferring human genes into respiratory chain-deficient fibroblasts, followed by a metabolic selection in a highly selective medium. We used a normalized expression cDNA library in an episomal vector (pREP4) to transfect the fibroblasts, and a medium with glutamine and devoid of any carbohydrate source to select metabolically.