The deleterious recurrent frameshift insertion mutation (NM_001379659.1: c.3755dup) in the ZNF142 gene leads to intellectual developmental disorder with impaired speech in three affected siblings with family history of same condition. The data have implications for genetic diagnosis and counseling in families with the same disorders.

In this work, we reported a 13-month-old Chinese Han male characterized by epileptic seizure, psychomotor development delay, muscular hypotonia, mild hydronephrosis in left kidney, liver and cardiac involvement. It was interesting that a novel variant was found in the ALG1 gene of the patient, which may extend the variant spectrum of ALG1 gene in ALG1-CDG. Furthermore, we also conducted a literature review to study whether disease severity of ALG1-CDG is associated with clinical manifestations or gene variants of individual, which has not been studied yet.

ELOVL4-related ichthyosis, spastic quadriplegia and mental retardation (ISQMR) is a rare autosomal recessive disorders characterized by ichthyosis with neurological features. Only five families with ISQMR with biallelic single-nucleotide variants have been described date and no families with copy number variants (CNVs) have been described. We include four new families with ISQMR, including two that carry a biallelic CNV and originate from the same tribe suggesting a tribal founder variant.

This work describes our cross-disciplinary experience identifying and evaluating 12 patients for clinical, biochemical, and familial features of Hypophosphatasia (HPP) from a retrospective database review of expanded carrier screening (ECS) results in our center. Completion of clinical questionnaire and in-person evaluations of 10/12 ECS-identified ALPL heterozygotes revealed all had features consistent with HPP. This is particularly poignant for those providers in OB/GYN and Maternal-Fetal Medicine settings who are facing incidentally diagnostic ECS results in seemingly healthy adults pursuing ECS for reproductive risk assessment, as persons with HPP have unique bone health management needs.

Some clinically important genes and variants are not easily detected with standard next-generation sequencing (NGS) methods due to technical challenges arising from high-similarity copies, repetitive short sequences, and other complexities. When the chemistries and bioinformatics of NGS are jointly refined, even technically challenging genes and variants can be evaluated, including the Gaucher disease-associated GBA, which has a high-similarity pseudogene.