Deciphering the molecular landscape of microcephaly in 87 Indian families by exome sequencing

We present data of 91 patients from 87 unrelated families referred to our clinic during 2016-2020 and provide a comprehensive clinical and genetic landscape in the studied cohort. Molecular diagnosis using exome sequencing was made in 45 families giving a yield of 51.7%. In 9 additional families probable causative variants were detected. We identified disease causing variations in 49 genes that are involved in different functional pathways Among these, 36 had an autosomal recessive pattern, 8 had an autosomal dominant pattern (all inherited de novo), and 5 had an X-linked pattern. In 41 probands where sequence variations in autosomal recessive genes were identified 31 were homozygotes (including 16 from non-consanguineous families). The study added 28 novel pathogenic/likely pathogenic variations. The study also calls attention to phenotypic variability and expansion in spectrum as well as uncovers genes where microcephaly is not reported previously or is a rare finding. We here report phenotypes associated with the genes for ultra-rare NDDs with microcephaly namely ATRIP, MINPP1, PNPLA8, AIMP2, ANKLE2, NCAPD2 and TRIT1.PMID:35568357 | DOI:10.1016/j.ejmg.2022.104520

Source: European Journal of Medical Genetics - May 14, 2022 Category: Genetics & Stem Cells Authors: Suzena Masih Amita Moirangthem Arya Shambhavi Archana Rai Kausik Mandal Deepti Saxena Mayank Nilay Neha Agrawal Somya Srivastava Haseena Sait Shubha R Phadke Source Type: research