Co-occurrence of Aicardi-Goutières syndrome type 6 and dyschromatosis symmetrica hereditaria due to compound heterozygous pathogenic variants in ADAR1: a case series from India.

Aicardi-Goutières syndrome type 6 (AGS6) and dyschromatosis symmetrica hereditaria (DSH) are allelic disorders caused respectively by biallelic and heterozygous pathogenic variants in ADAR1. We report three unrelated children presenting with features of both AGS6 and DSH, two of whom had compound heterozygous pathogenic variants in ADAR1. We also describe the novel genetic variants in our cases and review the literature on association of ADAR1-related AGS6 and DSH with these phenotypes.

Molecular analyses of novel ASAH1 mutations causing Farber lipogranulomatosis: analyses of exonic splicing enhancer inactivating mutation.

Farber lipogranulomatosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the ASAH1 gene. In the largest ever study, we identified and characterized ASAH1 mutations from 11 independent Farber disease (FD) families. A total of 13 different mutations were identified including 1 splice, 1 polypyrimidine tract (PPT) deletion and 11 missense mutations. Eleven mutations were exclusive to the Indian population. The IVS6+4A>G splice and IVS5-16delTTTTC PPT deletion mutations resulted in skipping of exon 6 precluding thereby the region responsible for cleavage of enzyme precursor. A missense mutation (p.V198A) resulted in skipping of exon 8 due to inactivation of an exonic splicing enhancer (ESE) element. This is the first report of mutations affecting PPT and ESE in the ASAH1 gene resulting in FD.

Tel Hashomer camptodactyly syndrome: a case report.

Tel Hashomer camptodactyly syndrome (THCS) is a rare autosomal recessive camptodactyly with muscular involvement. The manifestations of THCS other than camptodactyly are clubbed feet, thenar and hypothenar hypoplasia, abnormal palmar creases and dermatoglyphic ridges, spina bifida and mitral valve prolapse. The syndrome was first described by Goodman et al in 1972 and thereafter two further cases with similar phenotype were seen. Herein, we present another case report and review of the literature of other syndromes associated with camptodactyly and mitral valve prolapse. Further cases with this syndrome need to be reported for mapping of the candidate loci. This will help in planning management and genetic counselling.

Tel hashomer camptodactyly syndrome a case report / El síndrome de camptodactilia de tel hashomer un reporte de caso

Tel Hashomer camptodactyly syndrome (THCS) is a rare autosomal recessive camptodactyly with muscular involvement. The manifestations of THCS other than camptodactyly are clubbed feet, thenar and hypothenar hypoplasia, abnormal palmar creases and dermatoglyphic ridges, spina bifida and mitral valve prolapse. The syndrome was first described by Goodman et al in 1972 and thereafter two further cases with similar phenotype were seen. Herein, we present another case report and review of the literature of other syndromes associated with camptodactyly and mitral valve prolapse. Further cases with this syndrome need to be reported for mapping of the candidate loci. This will help in planning management and genetic counselling.

El síndrome de camptodactilia de Tel Hashomer (SCTH) es una camptodactilia autosómica recesiva rara con compromiso muscular. Las manifestaciones de SCTH, aparte de la camptodactilia, son: pies equinovaros (zambos), hipoplasia tenar e hipotecar, pliegues palmares anormales, y dermatoglifos, espina bífida, y prolapso de la válvula mitral. El síndrome fue descrito por primera vez por Goodman et al en 1972, tras lo cual se vieron otros dos casos con fenotipos similares. Aquí presentamos otro reporte de caso, y revisamos la literatura de otros síndromes asociados con camptodactilia y el prolapso de la válvula mitral. Se necesitan reportes de otros casos con este síndrome para hacer el mapa de los locus candidatos. Esto ayudará a planear el tratamiento y a decidir el asesoramiento genético.

Four common glomulin mutations cause two thirds of glomuvenous malformations ("familial glomangiomas"): evidence for a founder effect.

BACKGROUND: Glomuvenous malformation (GVM) ("familial glomangioma") is a localised cutaneous vascular lesion histologically characterised by abnormal smooth muscle-like "glomus cells" in the walls of distended endothelium lined channels. Inheritable GVM has been linked to chromosome 1p21-22 and is caused by truncating mutations in glomulin. A double hit mutation was identified in one lesion. This finding suggests that GVM results from complete localised loss of function and explains the paradominant mode of inheritance. OBJECTIVE: To report on the identification of a mutation in glomulin in 23 additional families with GVM. RESULTS: Three mutations are new; the others have been described previously. Among the 17 different inherited mutations in glomulin known up to now in 43 families, the 157delAAGAA mutation is the most common and was present in 21 families (48.8%). Mutation 108C-->A was found in five families (11.8%), and the mutations 554delA+556delCCT and 1179delCAA were present together in two families (4.7% each). Polymorphic markers suggested a founder effect for all four mutations. CONCLUSIONS: Screening for these mutations should lead to a genetic diagnosis in about 70% of patients with inherited GVM. So far, a mutation in glomulin has been found in all GVM families tested, thus demonstrating locus homogeneity.