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Abstract <p>The Mannosidase Alpha class 1B member 1 (<i>MAN1B1</i>) Gene encodes the endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (ERManI) protein, which is thought to be crucial for the degradation of misfolded glycoproteins. Although there were differences in clinical features across individuals, but most patients reported had truncal obesity, facial dysphormaties, and mild to moderate intellectual disability. While the <i>CAPN10</i> gene encodes cysteine protease calpain-10 is an intracellular protease (calcium-dependent) expressed ubiquitously in several tissues and involved in secretions of pancreatic β-cell insulin, translocating glucose transporter 4 to the cell membrane of adipocytes and thermogenesis. Genetic variants in <i>CAPN10</i> cause diabetes type II (T2DM), obesity, and mild to moderate intellectual disability. Here, we describe the affected individuals of two different Pakistani families segregating with syndromic disorders showing clinical features of truncal obesity, motor developmental delay, and mild intellectual disability in one of the families while obesity, diabetes, and mildintellectual disability in the other family. Whole exome sequencing and Sanger sequencing led to identification of 22 bp exonic deletion in <i>MAN1B1</i> (c.1833_1854del; Asp613Alafs*108) and a homozygous missense substitution in <i>CAPN10</i> (c.136C&gt;G; p.Pro46Ala). Our results not only expand the mutational spectrum of <i>MAN1B1</i> and <i>CAPN10</i>, but also provide deeper insights by documenting clinical features and genetics findings and would prove to be a valuable addition to genetic diagnostics procedures.</p>

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Exonic Deletion in MAN1B1 and a Missense Substitution in CAPN10 Causes Truncal Obesity, Type 2 Diabetes, Delayed Motor Development and Mild Intellectual Disability

  • 期刊论文

  • 发表日期：

    2025年6月26日

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  • S. Naudhani,
  • F. K. Bazai,
  • A. Ahmad,
  • H. Tayyab,
  • M. T. Pervez,
  • A. Zafar,
  • S. A. Shah,
  • N. Raheem,
  • M. Tariq,
  • M. Saleem,
  • R. Sheikh,
  • S. Daud

摘要

Abstract

The Mannosidase Alpha class 1B member 1 (MAN1B1) Gene encodes the endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (ERManI) protein, which is thought to be crucial for the degradation of misfolded glycoproteins. Although there were differences in clinical features across individuals, but most patients reported had truncal obesity, facial dysphormaties, and mild to moderate intellectual disability. While the CAPN10 gene encodes cysteine protease calpain-10 is an intracellular protease (calcium-dependent) expressed ubiquitously in several tissues and involved in secretions of pancreatic β-cell insulin, translocating glucose transporter 4 to the cell membrane of adipocytes and thermogenesis. Genetic variants in CAPN10 cause diabetes type II (T2DM), obesity, and mild to moderate intellectual disability. Here, we describe the affected individuals of two different Pakistani families segregating with syndromic disorders showing clinical features of truncal obesity, motor developmental delay, and mild intellectual disability in one of the families while obesity, diabetes, and mildintellectual disability in the other family. Whole exome sequencing and Sanger sequencing led to identification of 22 bp exonic deletion in MAN1B1 (c.1833_1854del; Asp613Alafs*108) and a homozygous missense substitution in CAPN10 (c.136C>G; p.Pro46Ala). Our results not only expand the mutational spectrum of MAN1B1 and CAPN10, but also provide deeper insights by documenting clinical features and genetics findings and would prove to be a valuable addition to genetic diagnostics procedures.