0000000000383390
AUTHOR
Nicolai Kohlschmidt
Adipositaschirurgie bei monogenetisch bedingter Adipositas
Surgical treatment of patients suffering from monogenetic forms of morbid obesity is considered to be the poorest investigated theme in bariatric surgery. This review article presents aspects of genetic disorders in morbid obesity as well as some aspects of surgical treatment in patients with monogenetic forms of morbid obesity (Prader-Willi-Syndrome). Gastric restrictive procedures such as vertical banded gastroplasty or adjustable gastric banding as well as malabsorptive and mix procedures such as biliopancreatic diversion or Roux-en-Y gastric bypass are used for treatment, similar to polygenetic forms of morbid obesity. Until to now there is no evidence-based data because of the small nu…
Newborn screening for 3-methylcrotonyl-CoA carboxylase deficiency: population heterogeneity of MCCA and MCCB mutations and impact on risk assessment.
New technology enables expansion of newborn screening (NBS) of inborn errors aimed to prevent adverse outcome. In conditions with a large share of asymptomatic phenotypes, the potential harm created by NBS must carefully be weighed against benefit. Policies vary throughout the United States, Australia, and Europe due to limited data on outcome and treatability of candidate screening conditions. We elaborated the rationale for decision making in 3-methylcrotonyl-coenzyme A (CoA) carboxylase deficiency (MCCD), which afflicts leucine catabolism, with reported outcomes ranging from asymptomatic to death. In Bavaria, we screened 677,852 neonates for 25 conditions, including MCCD, based on elevat…
Expression of somatic DNA repair genes in human testes
Meiosis is the key process for recombination and reduction of the diploid chromosome set to a haploid one. Many genes that have been found in yeast or mouse models to play a role in meiosis are also important for the repair of DNA damage in somatic cells. To study the DNA repair gene transcriptome during male germ cell development, we have developed a specialized cDNA microarray with 181 human genes which are involved in different somatic DNA repair pathways and/or cell cycle control and 45 control house-keeping genes. This DNA repair gene chip was used to quantify the mRNA expression levels in three human testes samples versus a fibroblast RNA pool. Two hundred twenty genes on the chip (in…
Case report supporting that the Barber-Say and ablepharon macrostomia syndromes could represent one disorder.
We report on a 7-year-old girl with unequivocal features of Barber-Say syndrome (BSS): generalized hypertrichosis especially at the back, dry lax skin, macrostomia, thin lips, cup-shaped ears, bulbous nose, hypoplastic nipples, and abnormal external genitalia. She also demonstrated conductive hearing impairment and microblepharon. BSS has been reported with ectropion (not present in our patient), but ablepharon and microblepharon (i.e., absent or hypoplastic eyelids) have always been considered as hallmarks of ablepharon macrostomia syndrome (AMS). This is the first report of microblepharon in BSS. Other authors have discussed that BSS and AMS could possibly represent one syndrome, and our …
Linkage disequilibrium of MTHFR genotypes 677C/T-1298A/C in the German population and association studies in probands with neural tube defects(NTD).
A number of studies have demonstrated that the common polymorphism 677CT in the gene encoding 5, 10-methylenetetrahydrofolate reductase (MTHFR) leads to a thermolabile variant with decreased enzyme activity and to mildly elevated plasma homocysteine. 677TT homozygosity was shown to be more frequent in NTD probands compared with controls in some studies. Recently, another polymorphism, 1298AC, in the MTHFR gene was described and combined heterozygosity 677CT/1298AC was suggested to be an additional risk factor for NTD. The present study examines the genotype and haplotype distribution of the two polymorphisms in the German population and evaluates the impact on NTD individuals and their rela…
Homozygous disruption of PDZD7 by reciprocal translocation in a consanguineous family: a new member of the Usher syndrome protein interactome causing congenital hearing impairment.
A homozygous reciprocal translocation, 46,XY,t(10;11),t(10;11), was detected in a boy with non-syndromic congenital sensorineural hearing impairment. Both parents and their four other children were heterozygous translocation carriers, 46,XX,t(10;11) and 46,XY,t(10;11), respectively. Fluorescence in situ hybridization of region-specific clones to patient chromosomes was used to localize the breakpoints within bacterial artificial chromosome (BAC) RP11-108L7 on chromosome 10q24.3 and within BAC CTD-2527F12 on chromosome 11q23.3. Junction fragments were cloned by vector ligation and sequenced. The chromosome 10 breakpoint was identified within the PDZ domain containing 7 (PDZD7) gene, disrupti…
<i>GJB2</i> Mutations and Genotype-Phenotype Correlation in 335 Patients from Germany with Nonsyndromic Sensorineural Hearing Loss: Evidence for Additional Recessive Mutations Not Detected by Current Methods
We report on 335 patients (319 families) with mild-to-profound nonsyndromic sensorineural hearing loss. We identified 178 mutated <i>GJB2</i> alleles representing 29 different sequence changes (including 3 novel mutations: Q7P, N14D, H100Q), and 2 alleles with the deletion del(GJB6-D13S1830) of the <i>GJB6</i> gene. Eleven <i>GJB2</i> mutations (119 mutated alleles) were truncating (T), and 18 mutations (59 alleles) were nontruncating (NT). Biallelic <i>GJB2</i> mutations were found in 71 patients (21.2%; 67 families; 25 different genotypes). Audiograms of 62 patients (56 families) with biallelic <i>GJB2</i> mutations typically ind…
Familial Sotos syndrome caused by a novel missense mutation, C2175S, in NSD1 and associated with normal intelligence, insulin dependent diabetes, bronchial asthma, and lipedema
We report a familial Sotos syndrome in two children, boy and girl, aged 17 and 8 years, and in their 44 year old mother, who displayed normal intelligence at adult age, but suffered from insulin dependent diabetes mellitus, bronchial asthma, and severe lipedema. The underlying missense mutation, C2175S, occurred in a conserved segment of the NSD1 gene. Our findings confirm that familial cases of SS are more likely to carry missense mutations. This case report may prove useful to avoid underestimation of the recurrence rate of SS, and to demonstrate that the developmental delay may normalize, enabling an independent life and having an own family.
Syndrome of autosomal recessive polycystic kidneys with skeletal and facial anomalies is not linked to the ARPKD gene locus on chromosome 6p
We report on two sibs, both males, one born at 37 the other at 24 weeks of gestation, both with a syndrome similar to that seen in three sets of sibs by Gillessen-Kaesbach et al. [1993: Am J Med Genet 45:511–518]. Both propositi had polycystic kidneys and hepatic fibrosis indistinguishable from that seen in autosomal recessive polycystic kidney disease (ARPKD), and skeletal and facial anomalies. Skeletal abnormalities included “butterfly” vertebrae, square shape of pelvis, and brachymelia. The facial anomalies included hypertelorism, epicanthic folds, and anteverted nares. Additional external findings were apparently low-set ears and a short neck. Histopathological examination of the kidney…
Epimutation at human chromosome 14q32.2 in a boy with a upd(14)mat-like clinical phenotype.
Recently, three reports described deletions and epimutations affecting the imprinted region at chromosome 14q32.2 in individuals with a phenotype typical for maternal uniparental disomy of chromosome 14 [upd(14)mat]. In this study, we describe another patient with upd(14)mat-like phenotype including low birth weight, neonatal feeding problems, muscular hypotonia, motor and developmental delay, small hands and feet, and truncal obesity. Conventional cytogenetic analyses, fluorescence in situ hybridization subtelomere screening, multiplex ligation-dependent probe amplification analysis of common microdeletion and microduplication syndromes, and methylation analysis of SNRPN all gave normal re…
Deficient membrane integration of the novel p.N14D-GJB2mutant associated with non-syndromic hearing impairment
Mutations in GJB2, the gene encoding for the Gap Junction protein Connexin 26 (Cx26), have been established as the major cause of hereditary, non-syndromic hearing impairment (HI). We report here the identification of a novel point mutation in GJB2, c.40A>G [p.N14D], detected in compound heterozygosity with the c.35delG mutation in two brothers with moderate non-syndromic sensorineural HI. The mother who carried one wildtype and a p.N14D allele displayed normal hearing. The mutation leads to substitution of the neutral amino acid asparagine (N) by the negatively charged aspartic acid (D) at amino acid number 14, a position that is conserved among Cx26 of different organisms and among many o…
Familial fatal fetal cardiomyopathy with isolated myocardial calcifications: A new syndrome?
We describe three male sib fetuses with isolated myocardial calcifications resulting in intrauterine fetal death (IUFD) as early as the second trimester. No evidence for an underlying mitochondrial cytopathy, dystrophinopathy or myopathy was found. There were no signs of inflammation or a metabolic disorder, and the mother had no prenatal exposure of teratogenic drugs. Furthermore, no mutation in the Barth syndrome gene (G4.5) could be detected. Because isolated calcification of the heart and IUFD are not typical of any previously described inherited cardiomyopathy, it may represent a new familial fetal cardiomyopathy.