The cover image is based on the Clinical Report Novel hemizygous single-nucleotide duplication in RPGR in a patient with retinal dystrophy and sensorineural hearing loss by Ryan J. German et al., https://doi.org/10.1002/mgg3.2404

pc-MINI vector detection results. (A) Construction of the pcMINI-SLC26A4-wt/mut vector harboring exon6 and flanking intronic sequences from WT or Mut types (c.765+4A>G) of the SCL26A4 gene. (B) Minigene construction sequencing map, Wt on top and Mut on bottom; (C) RT-PCR products were separated by electrophoresis of the pcMINI-SLC26A4-wt/mut vector in HeLa and c293T cells. (D) The different splicing products for wild-type (a, 554 bps) and variant type (b, 389 bps) are shown on 2% agarose gel electrophoresis and represented graphically, lane b was smaller than the lane a, and the migration was faster. (E) Corresponding sequencing results of shear bands. Red * indicates the mutation position.

Genetic screening by multicolor melting curve analysis combined with hearing screening is profit to diagnosis of hearing loss of neonates.

We here report a Chinese patient with Intellectual Developmental Disorder (IDD), autosomal recessive 57. Two previously unreported mutations in MBOAT7, c.669C>G (p.(Y223*)) and c.1095C>G (p.(S365R)) were identified by trio whole-exome sequencing. The patient we reported here is the first Han Chinese IDD patient known to be related to MBOAT7 mutation. In addition, this patient is the first case that carried compound heterozygous variants in the MBOAT7 gene, which expands the complexity of this disorder.

Male partners of women with RPL showed poorer semen quality and altered hormonal profile. Multiplex-PCR revealed microdeletions in AZFb (sY134), significantly more prevalent in RPL-men (16.7%) versus controls (p < 0.001). Y chromosome microdeletions provide valuable biomarkers, complementing semen and hormone analyses for identifying male factor contributions in couples with idiopathic RPL.

(A) No obvious chromosome aberration was found in the affected individuals. (B) Direct sequencing of PTHLH exons showing heterozygous c.146dupA, p.S50Vfs*22 mutation identified in BDE affected individuals (II2, III6, III16, III17, IV11) but not in normal family members (III5, IV2). (C) Evolutionary conservation of the cluster across multiple species.

Three exonic variants in the COL4A5 gene alter RNA splicing in a minigene assay. Two missense variants positioned the first nucleotides of the 5′ end of COL4A5 exons and one internal exonic nonsense variant caused aberrant splicing. Emphasized the necessity of assessing the effects of SNVs at the mRNA level.

Genotype analysis of two products of conception, from a couple with eight consecutive miscarriages and no live birth, demonstrated their triploid digynic genomes and maternal Meiosis I and II errors. Exome sequencing narrowed down the search for the causative gene to two genes, EIF4ENIF1 and HORMAD2. The presence of meiotic errors are in favor of the causal role of HORMAD2 in the causation of RM. This figure was created with BioRender.com.

Gain-of-function (GOF) variants of STAT3 cause early-onset multiorgan autoimmunity. In this study, we described a patient with early-onset diabetes, hypothyroidism, enteropathy, and postnatal short stature. Of note, the chronic diarrhea lasted 3 years and resolved spontaneously. We identified a novel STAT3 GOF variant p.E357K. Further functional data showed that the variant caused dysregulation of insulin gene expression through inhibition of the transcription factor ISL1.

In this article, we investigate the pathogenesis of two unrelated Chinese children who exhibited developmental delay/intellectual disability, delayed speech, attention deficit and hyperactivity disorder, behavioral abnormalities, short stature, low body weight, café-au-lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures. Two novel de novo likely pathogenic or pathogenic TNRC6B variants c.335C>T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63) were found in these patients. This study expands the genetic and phenotype spectrum of TNRC6B deficiency syndrome.

In this study, we present a case with less pigmented hair and fairer than normal skin. Strabismus, hyperopia, astigmatism and the absence of iris pigment were found in his both eyes. Whole exome sequencing was performed in all samples, and Sanger sequencing was then used to verify the mutations. Compound heterozygous variants, c.1304C>A (p.S435Y) and c.301C>G (p.R101G) in SLC45A2 gene, were detected proband. We emphasize that this compound heterozygous mutation case of OCA4 was the first report from China.

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.

The patient presented with X-linked ID identified a novel splicing variant in the CNKSR2 gene (c.1657+1G>A) by exome sequencing. The variant caused a 166 bp intron retention between exon 14 and 15, which was validated by Minigene assay.

Here, we report a new and rare homozygous variant identified from two children from one family in MLC1 which was also investigated its role on protein by experiment.

Comprehensive genetic testing is a powerful tool for diagnosis in medically underserved populations. After other smaller genetic tests were nondiagnostic, provision of whole exome sequencing through the Texome Project uncovered a novel likely pathogenic variant in RPGR that explains some of the patient phenotypes.

Variants in Aristaless-related homeobox (ARX) gene lead to a variety of phenotypes with intellectual disability being a steady feature. Other features can include severe epilepsy, spasticity, movement disorders, hydranencephaly, and ambiguous genitalia in males. Ohtahara syndrome or Type 1 early infantile epileptic encephalopathy is a severe early-onset epileptic encephalopathy with arrest of psychomotor development caused by hemizygous mutations in the ARX gene, which encodes a transcription factor in fundamental brain developmental processes. We presented a case report of 2-year-old boy, which indicates symptoms of Ohtahara syndrome.