Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2.

Purpose: The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood.

Methods: Genetic and clinical details of new and published individuals with pathogenic KDM6A variants were compiled and analyzed.

Results: Sixty-one distinct pathogenic KDM6A variants (50 truncating, 11 missense) from 80 patients (34 males, 46 females) were identified.

Histone H3.3 beyond cancer: Germline mutations in cause a previously unidentified neurodegenerative disorder in 46 patients.

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported.

Expanding the molecular spectrum and the neurological phenotype related to CAMTA1 variants.

The CAMTA1-associated phenotype was initially defined in patients with intragenic deletions and duplications who showed nonprogressive congenital ataxia, with or without intellectual disability. Here, we describe 10 individuals with CAMTA1 variants: nine previously unreported (likely) pathogenic variants comprising one missense, four frameshift and four nonsense variants, and one missense variant of unknown significance. Six patients were diagnosed following whole exome sequencing and four individuals with exome-based targeted panel analysis.

MAGEL2-related disorders: A study and case series.

Pathogenic MAGEL2 variants result in the phenotypes of Chitayat-Hall syndrome (CHS), Schaaf-Yang syndrome (SYS) and Prader-Willi syndrome (PWS). We present five patients with mutations in MAGEL2, including the first patient reported with a missense variant, adding to the limited literature. Further, we performed a systematic review of the CHS and SYS literature, assess the overlap between CHS, SYS and PWS, and analyze genotype-phenotype correlations among them.

Risks of reproducing with a genetic disorder.

Male-factor infertility is the cause of reproductive issues in many couples. For approximately 15% of these men, the origin of the infertility is genetic. These causes include both chromosomal and single-gene disorders frequently impacting spermatogenesis.