Molecular Genetics & Genomic Medicine

The deleterious recurrent frameshift insertion mutation (NM_001379659.1: c.3755dup) in the ZNF142 gene leads to intellectual developmental disorder with impaired speech in three affected siblings with family history of same condition. The data have implications for genetic diagnosis and counseling in families with the same disorders.

We highlight the life-threatening presentation of SMVT deficiency. Increased and isolated excretion of urinary 3-hydroxyisovaleric acid may suggest, in the absence of markedly reduced biotinidase activity, a SMVT deficiency. Prompt supplementation with high doses of biotin and pantothenic acid should be initiated while awaiting results of SLC5A6 sequencing as this condition may be life-threatening and a high dose of these water-soluble vitamins seems harmless.

ELOVL4-related ichthyosis, spastic quadriplegia and mental retardation (ISQMR) is a rare autosomal recessive disorders characterized by ichthyosis with neurological features. Only five families with ISQMR with biallelic single-nucleotide variants have been described date and no families with copy number variants (CNVs) have been described. We include four new families with ISQMR, including two that carry a biallelic CNV and originate from the same tribe suggesting a tribal founder variant.

Overview of study design and results—Dysmorphic patients had a two-fold increased risk of having genetic disorders identified, consistent across extra cardiac anomalies (ECA) status. However, dysmorphic status as a screen for genetic disorders is limited due to 8% of genetic disorders missed due to not having ECA or noticeable dysmorphisms.

We conducted a retrospective study of 24 cases in a hospital in eastern China and found variants in several genes. Of note, we found a compound heterozygous mutation in UGDH. One of the mutations in the second exon has not been described previously. We performed a protein analysis of the structure and proposed that the mutated protein may be unstable. Our results add to the growing list of mutations that affect this gene. Since the condition responds poorly to antiepileptic therapy, increased single-gene mutations may aid in more targeted therapy.