Disease relevance of MKKS

• We and others have demonstrated that BBS6 is caused by mutations in the gene MKKS (refs. 12,13), mutation of which also causes McKusick-Kaufman syndrome (hydrometrocolpos, post-axial polydactyly, and congenital heart defects) [1].
• A female with complete lack of Müllerian fusion, postaxial polydactyly, and tetralogy of fallot: genetic heterogeneity of McKusick-Kaufman syndrome or a unique syndrome [2]?
• Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome [3].
• We report here a series of nine patients diagnosed in infancy with MKKS because of the presence of vaginal atresia and postaxial polydactyly, who later developed obesity and retinal dystrophy, thus turning out to be instances of BBS [4].
• McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos [5].

Psychiatry related information on MKKS

• The diagnosis of MKKS should be considered with caution in all published cases described exclusively in the neonatal period and in those with mental retardation [4].

High impact information on MKKS

• The BBS6 protein has similarity to a Thermoplasma acidophilum chaperonin, whereas BBS2 and BBS4 have no significant similarity to chaperonins [6].
• MKKS has sequence homology to the alpha subunit of a prokaryotic chaperonin in the thermosome Thermoplasma acidophilum [1].
• Mutations in MKKS cause Bardet-Biedl syndrome [7].
• McKusick-Kaufma syndrome (MKS) includes hydrometrocolpos, postaxial polydactyly and congenital heart disease, and is also inherited in an autosomal recessive manner [7].
• BBS12 is vertebrate specific and, together with BBS6 and BBS10, defines a novel branch of the type II chaperonin superfamily [8].

Biological context of MKKS

• We conclude that the "triallelic" model does not explain the incomplete penetrance of MKS [9].
• We have collected a cohort of 163 pedigrees from diverse ethnic backgrounds and have evaluated them for mutations in the recently discovered BBS6 gene (MKKS) on chromosome 20 and for potential assignment of the disorder to any of the other known BBS loci in the human genome [10].
• Consistent with an important centrosomal function, silencing of the BBS6 transcript by RNA interference in different cell types leads to multinucleate and multicentrosomal cells with cytokinesis defects [11].
• The restricted tissue distribution of BBS6 further suggests that it may play important roles in ciliated epithelial tissues, which is consistent with the probable functions of BBS proteins in basal bodies (modified centrioles) and cilia [11].
• During interphase, BBS6 is confined to the lateral surfaces of the PCM but during mitosis it relocalizes throughout the PCM and is found at the intercellular bridge [11].

Anatomical context of MKKS

• MKS is a rare, autosomal recessive lethal condition characterized by central nervous system malformations (typically, occipital meningoencephalocele), postaxial polydactyly, multicystic kidney dysplasia, and ductal proliferation in the portal area of the liver [12].
• Both MKS proteins predominantly localized to epithelial cells, including proximal renal tubules and biliary epithelial cells [13].
• We report on a case of duplicated hydrometrocolpos with uterus didelphys, a septate vagina, lower vaginal atresia, a persistent urogenital sinus, left ear agenesis, a single umbilical artery, and an imperforate anus, but without the associated features of McKusick-Kaufman syndrome such as polydactyly and congenital heart defects [14].
• This is a case presentation of a neonate with McKusick-Kaufman Syndrome (hydrometrocolpos, polydactyly and congenital heart disease) accompanied by a complete tracheal ring in the distal trachea [15].

Associations of MKKS with chemical compounds

• High-molecular-weight cytochromes (Hmcs) belong to a large family of multihaem cytochromes in sulfate-reducing bacteria [16].
• A reversed-phase liquid chromatographic method with coulometric detection has been developed for the determination of free MKS 213-492 (a novel xanthine derivative) in plasma [17].

Other interactions of MKKS

• However, mutations in MKKS are found in only 4%-11% of unselected Bardet-Biedl syndrome patients [18].
• The dual midline fusion defects of tetralogy of Fallot and MA suggests that either this patient has a unique syndrome with a distinct genetic etiology or that she has a genetically heterogeneous or variant form of MKS [2].
• The phenotypic triad of anomalies most closely resembled McKusick-Kaufman syndrome (MKS; OMIM 236700), a rare multiple congenital anomaly syndrome comprised of hydrometrocolpos (HMC), PAP, and congenital heart malformation that is inherited in an autosomal recessive pattern [2].
• Ten patients with EVC syndrome, one with McKusick-Kaufman syndrome, and one with OFD syndrome type II had AVCD [19].

Analytical, diagnostic and therapeutic context of MKKS

• In situ hybridization studies for MKS3 in early human embryos showed transcript localizations in agreement with the tissue phenotype of MKS patients [13].
• Molecular masses of both Hmcs determined by SDS-PAGE are 65 kDa [20].
• Determination of a novel xanthine derivative, MKS 213-492, in plasma by high-performance liquid chromatography with electrochemical detection [17].

References