Clinical and genetic investigation of 14 families with various forms of short stature syndromes

• Published in: Clinical genetics Vol. 106; no. 3; pp. 347 - 353
• Main Authors: Khan, Fati Ullah, Khan, Hammal, Ullah, Kifayat, Nawaz, Shoaib, Abdullah, Khan, Muhammad Javed, Ahmed, Sohail, Ilyas, Muhammad, Ali, Amjad, Ullah, Imran, Sohail, Aamir, Hussain, Shabir, Ahmad, Farooq, Faisal, Sufyan, Raza, Hayat, Amir, Hanif, Tooba, Bibi, Fatima, Hayat, Maria, Ullah, Rehmat, Khan, Inam Ullah, Ali, Raja Hussain, Hasni, Muhammad Sharif, Ali, Hamid, Bilal, Muhammad, Peralta, Susana, Buchert, Rebecca, Zehri, Zamrud, Hassan, Gul, Liaqat, Khurrum, Zahid, Muhammad, Shah, Khadim, Mikitie, Outi, Haack, Tobias B., Ji, Weizhen, Lakhani, Saquib A., Ansar, Muhammad, Ahmad, Wasim
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2024
• Subjects: disease‐causing variants; Gene mapping; homozygosity mapping; Population studies; Sanger sequencing; syndromic short stature; WES; Whole genome sequencing; disease‐causing variants; Sanger sequencing; WES; syndromic short stature; homozygosity mapping
• ISSN: 0009-9163; 1399-0004; 1399-0004
• DOI: 10.1111/cge.14550

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease‐causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population. In this study, families were approached in their hometowns to construct pedigrees and perform clinical evaluations. Subsequently, subjects were selected for genetic analysis to facilitate diagnosis. This comprehensive approach integrates familial history, clinical assessment, and genetic insights, enhancing our understanding of inherited disorders and informing personalized healthcare strategies.