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Hereditary ectodermal dysplasias are a complex group of inherited disorders characterised by abnormalities in two or more ectodermal derivatives (skin, nails, sweat glands, etc.). There are two main types of these disorders – hidrotic and hypohidrotic/anhidrotic ectodermal dysplasias. Hypohidrotic ectodermal dysplasia (HED) or Christ-Siemens-Touraine syndrome (OMIM: 305100) occurs in 1 out of 5000–10,000 births [19] and has an X-linked recessive inheritance pattern (X-linked hypohydrotic ectodermal dysplasia – XLHED) [2].The main cause of XLHED is a broad range of pathogenic variants in the EDA gene (HGNC:3157, Xq12-13) which encodes the transmembrane protein ectodysplasin-A [4]. We report here the case of a patient with a novel inherited allelic variant in the EDA gene – NM_001399.5:c.337C>T (p.Gln113*) – in the heterozygous state. Targeted family member screening was conducted and other carriers of this EDA gene pathogenic variant were identified and phenotypically characterised. The patient subsequently underwent in vitro fertilisation with preimplantation genetic testing for monogenic diseases (PGT-M).

Background: Androgen insensitivity syndrome (AIS) is a rare X-linked disorder due to mutations in the androgen receptor (AR) gene causing end-organ resistance to the androgenic hormone. Subjects and Methods: Genetic studies were carried out in two families by karyotype and targeted exome sequencing of the AR gene. Results: Two novel missense mutations were identified, p.L822P and p.P392S, in two families with complete androgen insensitivity (CAIS) and partial androgen insensitivity (PAIS), respectively. Both had 46, XY karyotype. The mother was a heterozygous carrier in PAIS and negative in CAIS. These two were novel mutations, reported for the first time, in the AR gene. In silico analysis predicted that both mutations were damaging. We reviewed the various reported Indian mutations in the AR gene. Conclusion: AR gene mutations cause a wide spectrum of disorders from CAIS to male infertility or primary amenorrhea. Early diagnosis is essential for gender assignment and further management, family counseling, and prenatal diagnosis.

Background: Androgen insensitivity syndrome (AIS) is a rare X-linked disorder due to mutations in the androgen receptor (AR) gene causing end-organ resistance to the androgenic hormone. Subjects and Methods: Genetic studies were carried out in two families by karyotype and targeted exome sequencing of the AR gene. Results: Two novel missense mutations were identified, p.L822P and p.P392S, in two families with complete androgen insensitivity (CAIS) and partial androgen insensitivity (PAIS), respectively. Both had 46, XY karyotype. The mother was a heterozygous carrier in PAIS and negative in CAIS. These two were novel mutations, reported for the first time, in the AR gene. In silico analysis predicted that both mutations were damaging. We reviewed the various reported Indian mutations in the AR gene. Conclusion: AR gene mutations cause a wide spectrum of disorders from CAIS to male infertility or primary amenorrhea. Early diagnosis is essential for gender assignment and further management, family counseling, and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: Androgen insensitivity syndrome or testicular feminization syndrome is a rare X-linked recessive disorder, which encompasses a wide range of phenotypes that are caused by numerous different mutations in the androgen receptor gene. Complete androgen insensitivity syndrome occurs when the body cannot use androgens at all. People with this form of the condition have the external sex characteristics of females, but do not have a uterus and therefore do not menstruate and are unable to conceive a child (infertile). Methods: In this paper, we report three cases of familial complete androgen insensitivity syndrome who presented with primary amenorrhea. Results: Physical examination, ultrasonography studies, and biochemical, karyotype, and molecular cytogenetic analyses were conducted. Based on the findings, they were diagnosed and confirmed as having complete androgen insensitivity syndrome. Conclusion: A multidisciplinary team is needed from disclosure of the diagnosis, gender assignment, surgical management, hormonal replacement therapy, to counseling and support. [ABSTRACT FROM AUTHOR]

Persons with unexplained early-onset stroke have been targeted for screening surveys for Fabry disease, the most common of the three X-linked lysosomal disorders, because Fabry patients with stroke are more likely to have the life-threatening progressive cardiac and renal manifestations and would therefore most benefit from early diagnosis and intervention with enzyme replacement therapy (ERT). Among 175 Israeli patients with unexplained cryptogenic stroke screened for mutations in the Fabry α galactosidase A (GLA) gene, sequencing identified six with 2–4 GLA intronic variants, one of whose father and three sisters had the same variants. Two variants, c.640-16A>G (g.10115A>G) in intron 4 and c.1000-22C>T (g.10956C>T) in intron 6, were common to all patients. However, three males with a common four variant intronic haplotype had low residual enzyme activity and ~ 50% reduced mRNA expression. Transcript splice-site defects were not identified in any of the index cases and X-chromosome inactivation was not highly skewed in the six females. These data do not suggest that GLA intronic variants, per se, are pathogenic. Nonetheless, it is clear that a certain intronic haplotype in males with cryptogenic stroke is associated with reduced GLA expression and function. [ABSTRACT FROM AUTHOR]

Wiskott Aldrich syndrome is an X-linked recessive disorder characterized by thrombocytopenia with microplatelets, eczema, recurrent infections, and predisposition to autoimmune disease and malignancy. It is a rare syndrome, and the incidence rate is approximately 4 in every 1 million live male births with no clear ethnic or racial predilection. The purpose of this paper was to report a case of Wiskott Aldrich syndrome with oral involvement demonstrated by 2 male siblings. [ABSTRACT FROM AUTHOR]

Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Background. Fabry disease, a lysosomal storage disease caused by deficient lysosomal α-galactosidase A activity, is characterized by globotriaosylceramide (GL-3) accumulation in multiple cell types, particularly the vasculature, leading to end organ failure. Accumulation in the kidney is responsible for progressive decline in renal function in male patients with the classical phenotype, resulting in renal failure in their third to fifth decades of life. With the advent of recombinant protein synthesis technology, enzyme replacement therapy has become a viable alternative to dialysis or renal transplantation, previously the only available treatment options for end-stage renal disease. Methods. The pre- and post-treatment renal biopsies were analyzed from fifty-eight Fabry patients enrolled in a Phase 3 double-blind, randomized, placebo-controlled trial followed by a six-month open label extension study of the recombinant human enzyme, α-galactosidase A (r-hαGalA), administered IV at 1 mg/kg biweekly. The purpose of this investigation was to detail the pathologic changes in glycosphingolipid distribution and the pattern of post-treatment clearance in the kidney. Results. Baseline evaluations revealed GL-3 accumulations in nearly all renal cell types including vascular endothelial cells, vascular smooth muscle cells, mesangial cells and interstitial cells, with particularly dense accumulations in podocytes and distal tubular epithelial cells. After 11 months of r-hαGalA treatment there was complete clearance of glycolipid from the endothelium of all vasculature as well as from the mesangial cells of the glomerulus and interstitial cells of the cortex. Moderate clearance was noted from the smooth muscle cells of arterioles and small arteries. Podocytes and distal tubular epithelium also demonstrated evidence for decreased... [ABSTRACT FROM AUTHOR]

X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by pathogenic variants in the BTK gene, resulting in impaired B cell differentiation and maturation. Over 900 variants have already been described in this gene, however, new pathogenic variants continue to be identified. In this report, we describe 22 novel variants in BTK , associated with B cell deficiency with hypo- or agammaglobulinemia in male patients or in asymptomatic female carriers. Genetic data was correlated with BTK protein expression by flow cytometry, and clinical and family history to obtain a comprehensive assessment of the clinico-pathologic significance of these new variants in the BTK gene. For one novel missense variant, p.Cys502Tyr, site-directed mutagenesis was performed to determine the impact of the sequence change on protein expression and stability. Genetic data should be correlated with protein and/or clinical and immunological data, whenever possible, to determine the clinical significance of the gene sequence alteration. [ABSTRACT FROM AUTHOR]

A 14-month-old boy with Menkes’ kinky hair syndrome (MS) associated with deafness and inferior cerebellar vermian hypoplasia was admitted with convulsions and urinary infection at Karadeniz Technical University, Trabzon, Turkey.

The results of carrier and prenatal diagnosis for Lesch-Nyhan syndrome by carrier testing of 83 women and prenatal analysis of 26 pregnancies are reported from the Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.

Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed.