In three different articles, a novel neurodevelopmental syndrome was described. It was characterised by intellectual disability, speech delay, ataxia and facial dysmorphism. Pathogenic variants in EBF3 were identified.
In a first article, the authors described an intellectual disability disorder in ten individuals with inherited or de novo monoallelic BRPF1 mutations. Symptoms included infantile hypotonia, global developmental delay, intellectual disability, expressive language impairment, and facial dysmorphism. Central nervous system and spinal abnormalities were also seen in some individuals.
In a second article, the authors performed exome sequencing in a large family affected by an autosomal-dominant form of mild syndromic intellectual disability with ptosis, growth retardation, and hypotonia, and identified a mutation in BRPF1 in five affected family members.
X-chromosome exome sequencing was performed to identify the genetic cause of syndromic intellectual disability in two unrelated families with suspected X-linked inheritance. In both families, affected males presented with severe intellectual disability, microcephaly, growth retardation, and epilepsy. A missense mutation and a frameshift mutation were identified in the EIF2S3 gene in the hemizygous state in affected patients, and in the heterozygous states female obligate carriers.
The authors reported bi-allelic pathogenic mutations in MDH2 in three unrelated subjects. They presented with early-onset generalised hypotonia, psychomotor delay, refractory epilepsy, and elevated lactate in the blood and cerebrospinal fluid.
The authors described a "thin" lissencephaly (TLIS) variant characterised by megalencephaly, frontal predominant pachygyria, intellectual disability, and seizures. Trio-based whole-exome sequencing and targeted re-sequencing identified recessive mutations of CRADD in six individuals with TLIS from four unrelated families of diverse ethnic backgrounds.
The authors investigated 7 male patients (from 5 different families) presenting with a new form of X-linked immunodeficiency characterised by profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a poor immune response to vaccine antigens, and increased susceptibility to bacterial and varicella zoster virus infections. They observed hemizygous mutations in the MSN gene (located on the X chromosome) in all 7 patients.
The authors reported two siblings who presented with failure to thrive, hypertriglyceridemia, developmental delay, liver dysfunction, lung cysts, and abnormal subcortical white matter. Using exome sequencing the siblings were found to harbour bi-allelic pathogenic-appearing variants within the YARS gene.
The aim of this study was to identify the causative mutation in a family with an unusual presentation of autosomal dominant osteopetrosis, proximal renal tubular acidosis, renal stones, epilepsy, and blindness, a combination of features not previously reported. A missense mutation in CLCN7 was identified.
Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase. Distinctive histopathology showed abundant internalised nuclei, myofibrillar disorganisation, desmin-positive inclusions, and thickened Z-bands.
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. One new GeneReviews has been published for:
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