Neal H Scherberg

Publications (3)12.99 Total impact

• Article: Autosomal dominant resistance to thyrotropin as a distinct entity in five multigenerational kindreds: clinical characterization and exclusion of candidate loci.

  Helmut Grasberger, Aviva Mimouni-Bloch, Marie-Christine Vantyghem, Guy van Vliet, Marc Abramowicz, Daniel L Metzger, Hussein Abdullatif, Catherine Rydlewski, Paolo E Macchia, Neal H Scherberg, Jacqueline van Sande, Marc Mimouni, Roy E Weiss, Gilbert Vassart, Samuel Refetoff
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  ABSTRACT: Resistance to TSH (RTSH) is an inherited disorder of variable hyposensitivity to TSH. The metabolic consequences can range from euthyroid hyperthyrotropinemia to severe congenital hypothyroidism with thyroid hypoplasia. Although subclinical and mild hypothyroidism fitting the RTSH phenotype is common in the population, the role of genetic factors is far from being understood. Only in rare cases has RTSH been attributed to TSHR or PAX8 gene mutations. OBJECTIVE, SETTING, AND PARTICIPANTS: Toward the identification of novel RTSH genes, we studied five large, unrelated families comprising 102 individuals, 56 of whom were affected. Inheritance of RTSH in these families followed an autosomal dominant pattern without evidence for incomplete penetrance, yet expressivity was variable. Considering only fully phenotyped generations, 64% of the progeny was affected, with a 1:1.4 male-to-female ratio. Of 18 affected individuals tested in the neonatal period, two were undetected because of borderline results. The thyroid phenotype was indistinguishable from that observed with PAX8 and TSHR defects. In four families, untreated affected subjects of all ages had elevated serum thyroglobulin levels, consistent with a defect in the thyroid follicle cells. Linkage of RTSH to TSHR and PAX8 was excluded in all five families. For the largest families, we likewise excluded a contribution of genes previously only associated with syndromic forms of RTSH, namely TITF1, GNAS, and FOXE1. These kindreds represent a distinct etiological entity of autosomal dominant RTSH. According to the clinical presentation of these families, genetic causes of mild hyperthyrotropinemia in the general population may be more common than currently appreciated.
  Journal of Clinical Endocrinology &amp Metabolism 08/2005; 90(7):4025-34. · 6.50 Impact Factor
• Article: Four new cases of congenital secondary hypothyroidism due to a splice site mutation in the thyrotropin-beta gene: phenotypic variability and founder effect.

  Guntram Borck, A Kemal Topaloglu, Eckhard Korsch, Ursula Martiné, Gabriele Wildhardt, Neslihan Onenli-Mungan, Bilgin Yuksel, Ulrich Aumann, Gerhard Koch, Guler Ozer, Roland Pfäffle, Neal H Scherberg, Samuel Refetoff, Joachim Pohlenz
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  ABSTRACT: Isolated TSH deficiency is a rare cause of congenital hypothyroidism. We here report four children from two consanguineous Turkish families with isolated TSH deficiency. Affected children who were screened at newborn age had an unremarkable TSH result and a low serum TSH level at diagnosis. Age at diagnosis and clinical phenotype were variable. All affected children carried an identical homozygous splice site mutation (IVS2 + 5 G--> A) in the TSHbeta gene. This mutation leads to skipping of exon 2 and a loss of the translational start codon without ability to produce a TSH-like protein. However, using specific monoclonal antibodies, we detected a very low concentration of authentic, heterodimeric TSH in serum, indicating the production of a small amount of correctly spliced TSH mRNA. By genotyping all family members with polymorphic markers at the TSHbeta locus, we show that the mutation arose on a common ancestral haplotype in three unrelated Turkish families indicating a founder mutation in the Turkish population. These results suggest that this TSHbeta mutation is among the more common TSHbeta gene mutations and stress the need for a biochemical and molecular genetic workup in children with symptoms suggestive of congenital hypothyroidism, even when the neonatal TSH screening is normal.
  Journal of Clinical Endocrinology &amp Metabolism 08/2004; 89(8):4136-41. · 6.50 Impact Factor
• Article: The preparation of carrier-free iodine isotope-substituted cytosine nucleotides

  Neal H. Scherberg, Samuel Refetoff
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  ABSTRACT: Cytosine nucleotide triphosphates can be iodinated with carrier-free iodine isotopes and separated from the parent compounds yielding products which have a 75 times (125I) or 550 times (131I) higher specific activity than commercially available tritium-labeled nucleotides. The iodine-containing nucleotides were substituted for the corresponding parent compounds in polymers synthesized by either DNA or RNA polymerase. Iodine-labeled nucleotides may be used to advantage in several types of investigation.
  Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis.