Portrait of Leopold Meyerhof in his World War I officer's uniform Military; World War I; Portraits

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Studio portrait of Paula Wallerstein nee Molling holding her infant daughter Karoline "Line".

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Studio portrait of Grete Lifmann nee Meyerhof Portraits Women

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Therese Molling with Joel, Ilse, Adolf, Grete, and Leopold Meyerhof on rooftop of store and residence Meyerhof am Platze; Hildesheim, Germany.

From left to right, standing: Ilse, Adolf, Grete and Lepold Meyerhof; from left to right, sitting: Joel Meyerhof and Therese Molling

Studio portrait of Paula Wallerstein nee Molling holding her infant daughter Karoline "Line".

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Margarete "Gretchen" Molling nee Benjamin holding her baby son Peter Adolf Molling.

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Studio portrait of Margarete "Gretchen" Molling nee Benjamin.

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Identification of two novel human neuronal ceroid lipofuscinosis genes

The neuronal ceroid lipofuscinoses (NCLs) are a group of mostly autosomal recessively inherited neurodegenerative disorders. The aim of this thesis was to characterize the molecular genetic bases of these, previously genetically undetermined, NCL forms. Congenital NCL is the most aggressive form of NCLs. Previously, a mutation in the cathepsin D (CTSD) gene was shown to cause congenital NCL in sheep. Based on the close resemblance of the phenotypes between congenital NCLs in sheep and human, CTSD was considered as a potential candidate gene in humans as well. When screened for mutations by sequencing, a homozygous nucleotide duplication creating a premature stop codon was identified in CTSD in one family with congenital NCL. While in vitro the overexpressed truncated mutant protein was stable although inactive, the absence of CTSD staining in brain tissue samples of patients indicated degradation of the mutant CTSD in vivo. A lack of CTSD staining was detected also in another, unrelated family with congenital NCL. These results imply that CTSD deficiency underlies congenital NCL. While initially Turkish vLINCL was considered a distinct genetic entity (CLN7), mutations in the CLN8 gene were later reported to account for the disease in a subset of Turkish patients with vLINCL. To further dissect the genetic basis of the disease, all known NCL genes were screened for homozygosity by haplotype analysis of microsatellite markers and/or sequenced in 13 mainly consanguineous, Turkish vLINCL families. Two novel, family-specific homozygous mutations were identified in the CLN6 gene. In the remaining families, all known NCL loci were excluded. To identify novel gene(s) underlying vLINCL, a genomewide single nucleotide polymorphism scan, homozygosity mapping, and positional candidate gene sequencing were performed in ten of these families. On chromosome 4q28.1-q28.2, a novel major facilitator superfamily domain containing 8 (MFSD8) gene with six family-specific homozygous mutations in vLINCL patients was identified. MFSD8 transcript was shown to be ubiquitously expressed with a complex pattern of alternative splicing. Our results suggest that MFSD8 is a novel lysosomal integral membrane protein which, as a member of the major facilitator superfamily, is predicted to function as a transporter. Identification of MFSD8 emphasizes the genetic heterogeneity of Turkish vLINCL. In families where no MFSD8 mutations were detected, additional NCL-causing genes remain to be identified. The identification of CTSD and MFSD8 increases the number of known human NCL-causing genes to eight, and is an important step towards the complete understanding of the genetic spectrum underlying NCLs. In addition, it is a starting point for dissecting the molecular mechanisms behind the associated NCLs and contributes to the challenging task of understanding the molecular pathology underlying the group of NCL disorders.

Studio portrait of Josef Molling with unidentified man; Heidelberg, Germany.

right: Joseph Molling sitting; left: unknown man standing

Studio portrait of Josef Molling with unidentified man; Heidelberg, Germany.

right: Joseph Molling sitting; left: unknown man standing

Portrait of Lena Molling nee Marx; Hannover, Germany.

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Portrait of Josef with his son Peter Molling.

Badly faded picture of Peter Molling, left, and his father, Josef Molling

Joseph Molling with wife Margarete "Gretchen" nee Benjamin and son Peter on a walk.

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Grave of Josef Molling; Germany.

Josef Molling committed suicide. He had financial problems, either embezzelment from the Prussian State Lottery or over an aircraft plant.

Portrait of Peter Molling and one unidentified child, playing in the sand; Germany.

left unknown child; right Peter Molling