View the August-September new syndromes list here.
New syndrome with retinitis pigmentosa is caused by nonsense mutations in RDH11 in three siblings
The authors investigated three siblings, born to asymptomatic parents, who each presented with atypical retinitis pigmentosa (RP) with systemic features, including facial dysmorphologies, psychomotor developmental delays recognized since early childhood, learning disabilities and short stature. RP-associated ophthalmological findings included salt-and-pepper retinopathy, attenuation of the arterioles and generalized rod–cone dysfunction. Atypical for RP features included mottled macula at an early age and peripapillary sparing of the retinal pigment epithelium. Whole-exome sequencing data identified compound heterozygous stop mutations in the RDH11 gene.
Familial syndrome of conduction system disease, atrial tachyarrhythmia and dilated cardiomyopathy due to TNNI3K mutation
The authors identified a familial syndrome of atrial tachyarrhythmia, conduction system disease, and dilated cardiomyopathy vulnerability. Seven members of a three-generation family exhibited the variably expressed phenotype. An unreported heterozygous missense mutation was found in TNNI3K.
Hypomyelination with spinal muscular atrophy and cerebellar hypoplasia caused by EXOSC8 mutations
The authors showed that homozygous missense mutations in EXOSC8 caused progressive and lethal neurological disease in 22 infants from three independent pedigrees. Affected individuals presented cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system or spinal motor neuron disease.
A human immunodeficiency reminiscent of APDS caused by heterozygous mutations in the PIK3R1 gene
The authors identified heterozygous mutations in PIK3R1 in four patients from three unrelated families diagnosed with hypogammaglobulinemia and recurrent infections. The immunological phenotype of these patients was heterogeneous and reminiscent of that observed in activated PIK3-delta syndrome (APDS). Various defects in the PI3K-triggered pathway could cause primary immunodeficiencies.
Novel syndrome of primordial dwarfism linked to NSMCE2 heterozygous frameshift mutations in two patients
The authors characterized two patients with primordial dwarfism, extreme insulin resistance, and gonadal failure. They identified compound heterozygous frameshift mutations in NSMCE2.
A new inborn error of metabolism affecting valine metabolism: ECHS1 mutations in Leigh disease
Two siblings with fatal Leigh disease had increased excretion of S-(2-carboxypropyl) cysteine and several other metabolites. In contrast to neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency (HIBCH deficiency), the excretion of 3-hydroxyisobutyryl-carnitine was normal in the children, suggesting deficiency of short chain enoyl-CoA hydratase (ECHS1 gene). Both children presented compound heterozygous mutations in ECHS1.
Patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness and peripheral neuropathy or with Leigh syndrome present an IARS2 mutation
The authors reported a novel disorder in three adult patients with a phenotype including cataracts, short stature secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral sensory neuropathy and skeletal dysplasia. They identified identified a homozygous missense mutation in IARS2 in affected patients. Compound heterozygous mutations in IARS2 were independently identified in a previously unreported patient with a more severe mitochondrial phenotype diagnosed as Leigh syndrome.
A hereditary bleeding disorder resulting from a premature stop codon in thrombomodulin
The authors identified three members of a family with a history of post-traumatic bleeding to be heterozygous for a novel thrombomodulin (THBD) mutation.
A severe skeletal dysplasia resulting from a novel dominant COL11A1 mutation in a family
The authors described a family with a severe skeletal dysplasia caused by a novel dominantly inheritedCOL11A1 mutation. Two siblings each presented with severe myopia, hearing loss, micromelia, metaphyseal widening of the long bones, micrognathia, and airway compromise requiring tracheostomy. Both died in early childhood because of tracheostomy dislodging or plugging. Their mother had mild rhizomelic shortening of the limbs, brachydactyly, and severe myopia; she was found mosaic for the COL11A1 mutation.
Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR
The authors identified a homozygous loss-of-function missense mutation in EGFR in a male infant with lifelong inflammation affecting the skin, bowel, and lungs. During the first year of life, his skin showed erosions, dry scale, and alopecia. Subsequently, there were numerous papules and pustules similar to the rash seen in patients receiving EGFR inhibitor drugs. The boy died at the age of 2.5 years from extensive skin and chest infections as well as electrolyte imbalance.
Severe developmental delay in a boy and a girl due to de novo missense mutations in the NAA10 gene
The authors identified de novo missense variants in NAA10 in two unrelated individuals, a boy and a girl, with severe global developmental delay and growth retardation but without any major dysmorphism.