Mutations in STAG1 were identified in 17 individuals from 16 families, 9 males and 8 females aged 2-33 years. The 17 patients shared common facial features, with wide mouth and deep-set eyes. Four individuals had mild microcephaly and seven had epilepsy.
The authors described a novel autosomal-recessive syndrome that included hydranencephaly (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly or MARCH). They used homozygosity mapping and exome sequencing to identify recessive mutations in a single family with three affected foetuses. They identified a homozygous nonsense mutation in CEP55 segregating with MARCH.
The authors described a new clinical entity, Sweeney-Cox syndrome, associated with distinct de novo amino acid substitutions in TWIST1, in two subjects with frontonasal dysplasia and additional malformations.
The authors reported on two families segregating with an autosomal recessive disorder characterised by generalised anhidrosis, severe heat intolerance and mild kidney failure. All affected individuals carried a rare homozygous missense mutation in CLDN10B.
Hyperinsulinemic hypoglycemia (HI) and congenital polycystic kidney disease (PKD) are rare, genetically heterogeneous disorders. The co-occurrence of these disorders (HIPKD) in 17 children from 11 unrelated families suggested an unrecognised genetic disorder. The authors found in all patients a promoter mutation in PMM2.
The authors sought the genetic cause of cardiac, vertebral, and renal defects, among others, in unrelated patients. They used genomic sequencing to identify potentially pathogenic gene variants in families in which a person had multiple congenital malformations. Variants were identified in HAAO and KYNU.
Recently, bi-allelic loss-of-function variants in SEMA3A were identified in a single patient with a particular pattern of multiple congenital anomalies. Using homozygosity mapping combined with exome sequencing, the authors identified a homozygous SEMA3A variant causing a premature stop codon in an 8-year-old boy with the same pattern of multiple congenital anomalies. The phenotype of these patients was characterised by postnatal short stature, skeletal anomalies of the thorax, a minor congenital heart or vascular defect, camptodactyly, micropenis, and variable additional anomalies. Motor development was delayed in both patients, and intellectual development was delayed in one patient.
Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, the authors recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome sequencing, they identified and characterised three rare loss-of-function variants in IFIH1. They concluded that IFIH1 deficiency causes a primary immunodeficiency manifested in extreme susceptibility to common respiratory RNA viruses.
A missense mutation in GPRASP2 gene was identified in four hemizygous male patients and two heterozygous female carriers from a Chinese family. The patients presented with an X-linked recessive syndromic hearing loss including ear anomalies, congenital conductive or mixed hearing loss and facial dysmorphism with bilateral ptosis.
The aim of that study was to describe the presentation and identify the cause of a new clinical phenotype, characterised by early severe neurodegeneration with myopathic and myasthenic features. Five patients showed severe muscular hypotonia, progressive cerebral atrophy, and therapy-refractory epilepsy. Three patients had congenital contractures. All patients died during their first year of life. In two of the patients, electrophysiologic testing showed abnormal decrement, but treatment with pyridostigmine led only to temporary improvement. Causative mutations in ALG14 were identified in all patients.
GeneReviews are expert-authored, peer-reviewed disease descriptions ("chapters") presented in a standardised format and focused on clinically relevant and medically actionable information on the diagnosis, management, and genetic counseling of patients and families with specific inherited conditions.
Four new GeneReviews have been published for:
Eight updated GeneReviews have been published for: