This study shows that a significant portion of the Pakistani population possesses at least one abnormal activity allele of the CYP2B6 gene, especially the frequency of the CYP2B6*6 variant is significant enough in the Pakistani population to be given an important consideration when drugs metabolized by this enzyme are prescribed.

The present study identify and characterize the variants underlying PKU in affected individuals in the Portuguese PKU/HPA cohort. Biochemical data, haplotic analysis and genetic findings performed in 223 patients diagnosed through the Portuguese Neonatal Screening Program (PNSP) is presented. The information obtained will improve the diagnostic applicability of mutational analysis and the capacity to predict the evolution of the disease.

Vanishing white matter (VWM) is a clinically highly variable leukodystrophy, caused by recessive mutations in eukaryotic initiation factor 2B (eIF2B)-subunit genes, mostly missense mutations. To gain insight into the strong genotype-phenotype correlation, we severity-graded 97 missense mutations using information from a clinical natural history study, created a new human eIF2B model structure by in silico modeling, and assessed mutated residues for location in subunits, eIF2B complex, and functional domains, and for information on biochemical activity. We demonstrated that mutations associated with (ultra-)severe disease mostly affect amino acids with pivotal roles in complex formation and eIF2B function, while mutations on the external eIf2B surface are mostly associated with mild phenotypes, probably because of minor functional effects. Therapies for VWM are emerging and reliable mutation-based phenotype prediction is required for propensity score matching for trials and individualized therapy decisions.

In this study, we have identified a family with two members affected by brachydactyly type A2 caused by BMPR1B mutation.

1. We report the detection of compound heterozygous mutations, c.80A>G mutation in SPINK5 gene in one allele and the ~275 Kb large-sized deletion mutation in another allele in a 3-year-old boy with Netherton syndrome.
2. After the intravenous immunoglobulin therapy, eruptions were improved remarkably in this patient with Netherton syndrome.

In this paper, we examined the phenotype of retinal organoids derived from a patient with non-syndromic CLN3 disease. We showed that accumulation of subunit C of mitochondrial ATPase occurs in patient retinal cells and cardiomyocytes, and could be prevented by gene correction. Additionally, we demonstrated that novel CLN3 transcripts are expressed in the human retina.

We report a female case of congenital cervical spinal muscular atrophy with Xp deletion. UBA1on this deleted segment is highly associated with major clinical features of this patient. This is the first study with evidence that CCSMA may be linked to a genetic cause.

DOCK7 deficiency causes a syndromic form of epileptic encephalopathy. Five children were previously reported. We report the disease outcome in two adult patients. All patients display biallelic truncating variants including a novel intragenic tandem duplication DOCK7 deficiency shown in cultured fibroblasts.

We used whole exome sequencing (WES) to investigate the pathogenic and likely pathogenic (PLP) variants in 10 individuals with HI, from four multiplex families from Cameroon, two of which were previously unresolved with a targeted gene enrichment (TGE) panel of 116 genes. All PLP variants previously identified with TGE were replicated. In one previously unresolved family, we found a homozygous frameshift PLP variant in GRXCR2 (OMIM: 615762), GRXCR2-c.251delC (p.Arg84 frameshift), in two affected siblings; and additionally, in 1/80 unrelated individuals affected with non-syndromic hearing impairment (NSHI). The GRXCR2-c.251delC variant introduced a premature stop codon, leading to truncation and loss of a zinc-finger domain. Fluorescence confocal microscopy tracked the wild-type GRXCR2 protein to the cellular membrane, unlike the mutated GRXCR2 protein. This study confirmsGRXCR2 as a HI-associated gene.

• The alloimmunization is the problem in 9.6% of sickle cell disease (SCD) and sickle thalassemia patients.
• The increase in the rate of alloimmunization was due to Rh alloantibodies.
• The Rh genotypes were different among sickle cell disease and sickle thalassemia patients than other populations and R1r′ and R0R1 genotypes were limited to our population.

A total of 53 participants (23 affected and 30 unaffected) from six unrelated Chinese families were recruited. Cataract phenotypes covered nuclear, total, posterior polar, pulverulent, snowflake-like, and zonular. Through targeted exome sequencing, six new mutations in four β-crystallin genes were revealed which included five missense mutations CRYBB1 p.Q70P, CRYBB2 p.E23Q, CRYBB2 p.A49V, CRYBB2 R188C, CRYBA4 p.M14K, and one splice mutation CRYBB3 c.75+1 G>A.

The genetically determined characteristics of enzymes of vitamin D metabolism may affect the Vit D levels in Tunisian SLE patients.

We report three Caucasiion siblings from non-consanguineous parents with novel compound heterozygous variants of TBXAS1 presenting with phenotypes of GHDD. Patient 1 and 2 are identical twins, who presented with red blood cell transfusion dependent normocytic anemia and thrombocytopenia with bone marrow fibrosis and cortical bone thickening of long bones on plain radiograph. Patient 3 is their sister with normal blood counts but cortical bone thickening on radiograph who has not required any treatment. These three cases illustrate the variable clinical expressivity of the GHDD from two-compound heterozygous pathogenic variants of TBXAS1.

We describe three unrelated patients with autism spectrum disorders and intellectual disabilities / developmental delay who are carriers of the 9p24.3 duplication including DOCK8 and KANK1. Clinical features of duplication are similar as 15q11.2 and 16p11.2 changes. We compared clinical features of patients with dupication 9p24.3, 15q11.2 and 16p11.2.

CAP+1 [A>C] (HBB:c.-50A>C) is a rare silent β-thalassemia (β-thal) mutation. We have for the first time the combination of CAP+1 [A>C] (HBB:c.-50A>C) mutation with β0 codon 5 [-CT] (HBB:c.17_18delCT) mutation in a Syrian proband. This combination leads to beta thalassemia intermedia (TI).

We firstly report three patients in a Chinese family with genetics diagnosis of TP63 translocation related with SHFM4. This identification expands our knowledge of genetic risk and counseling underlying SHFM.

All seven fetal cases in this report have 15q11-q13 microdeletions and microduplications of different sizes, but not all of them have clinical phenotypes or are clinically affected.

We present a novel SPINK5, likely pathogenic mutation in a patient with Netherton syndrome of Maltese-Caucasian ethnicity. We also tabulate the spectrum of documented SPINK5 mutations in this genodermatosis and discuss potential genotype–phenotype associations.

We describe a novel case of autosomal recessive Stickler syndrome caused by two undescribed loss of function mutations in the COL9A3 gene. Our patients have the more severe phenotype that included severe sensorineural hearing loss, high myopia, vitreoretinal degeneration, mild spondyloepiphyseal dysplasia, and early-onset arthropathy of the lower limbs.