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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. [ABSTRACT FROM AUTHOR]

Polydactyly or polydactylism, also known as a hyperdactyly, is a congenital limb defect with various morphologic phenotypes. Apart from physical and functional impairments, the presence of polydactyly is an indication of an underlying syndrome in the newborn. Usually, it follows as an autosomal dominant/recessive inheritance pattern with defects in the limb development's anteroposterior patterning. Although mutations in several genes have been associated with polydactyly; however, the exact underlying cause, pathways, and disease mechanisms are still unexplored, thus making it of multi‐factorial origin. Polydactyly is divided into three subtypes; radial, ulnar, and central polydactyly. So far, 11 loci (PAPA1‐PAPA11) and seven human genes have been reported to cause non‐syndromic postaxial polydactyly in humans, including the ZNF141, GLI3, IQCE, GLI1, FAM92A1, KIAA0825, and DACH1. In this review, we discuss emerging evidences of clinical and molecular characterization of polydactyly types in term of the involvement of newly associated genes and loci for non‐syndromic postaxial polydactyly, and how these might impact our understanding of the genetic mechanisms and molecular etiology involved in the cause of polydactyly. [ABSTRACT FROM AUTHOR]

Pre‐axial polydactyly (PPD) is characterized by well‐developed non‐functional 1st digit (thumb) duplication in hands and/or feet. It is mostly inherited in autosomal dominant manner. In the present study, two families of Pakistani origin, demonstrating unilateral PPD type A, have been characterized at clinical and genetic levels. Whole‐exome sequencing (WES) revealed a nonsense mutation (c.84C > A, p.Tyr28*) in the STKLD1, located on chromosome 9q34.2, in affected individuals of both the families. Our findings report the first direct involvement of the STKLD1 in the digit development and highlight the importance of inclusion of this gene for screening individuals presenting non‐syndromic recessive PPD. [ABSTRACT FROM AUTHOR]