Solving Medical Mysteries
Through Team Science

Claire’s Legacy: Inspiring Hope in the Face of the Unknown

After a healthy pregnancy and easy delivery, our first daughter and second child, Claire, was born on November 4, 2023 at 8:49 AM. Everything seemed fine. She had her first evaluation by the neonatologist and breastfed 6 times between her birth and 3:00 PM. Around 4:00 PM, our mother baby nurse just came into our room to check vitals and give Claire her first bath.  That’s when we noticed her very first episode. It looked like she could have been choking, but she was holding her breath and turning blue. When the nurse couldn’t get her to breathe on her own, she was rushed to the NICU and hooked up to oxygen. She had a few more episodes like this and was admitted to the NICU. Claire remained in St. Tammany Parish Hospital for 5 days, in a level 1 NICU, until her breathing got worse and she was transferred to Ochsner Baptist Hospital in New Orleans, where she was first intubated because they were no longer able to control her episodes. About 22 hours later, Dr. England, Ochsner Baptist Medical Director of the NICU, believed that Claire suffered from an unknown metabolic disease and had us transferred again to Children’s Hospital New Orleans to be under the care of Dr. Hans Anderson, Louisiana’s top genetic specialist. Many tests were done at Children’s Hospital. “At one point, 2 of 4 UOA have had significant amount of 3methlyglutaconic acid and 3-methylglutaric. When the Rapid Whole Genome to Gene DX came back entirely negative, Dr. Anderson had to re-look at 3MGA genes for VUS’s, etc. Nothing was found.”

Claire had her ups and downs while at Children’s Hospital. At one point in mid-December 2023, she was well enough for discharge, but she could not pass the swallow study, so we elected for a gastrostomy tube surgery so we could bring her home. Just a week later, she tested positive for COVID. Although she did not have any symptoms, her heart function deteriorated after she contracted this virus. On December 31, 2023, she had to have emergency surgery for pericardial effusion to remove fluid around her heart. The cardiac surgeon put a pericardial window and chest tubes to drain any excess fluid.

She passed away on January 29th, 2024, a few days shy of 3 months, in her parents’ loving arms. Claire’s side effects of this unknown metabolic disease include an enlarged heart, hypertrophic cardiomyopathy, pericardial effusion, elevated lactates, bilateral hearing loss, bilateral cataracts, and irregular brain function as shown on an EEG.

Our hope is that Claire’s story will be able to inspire others to never give up hope during difficult times, continue the search of answers of the unknown and eventually diagnose Claire’s disease, and help others who may suffer from this disease with a cure one day. Claire lived for a wonderful 87 days that we cherished so greatly; now we hope her legacy will live on forever with the help of each of you.

— Michael and Toni Guasco

The Undiagnosed Diseases Network at the ASHG 2021 Virtual Meeting

The Undiagnosed Diseases Network (UDN) is participating in the American Society of Human Genetics (ASHG) Virtual Meeting from October 18-22, 2021. Click here for a printable list of UDN talks and posters.

PLATFORM PRESENTATIONS

1153 ­ Bi-allelic variants in the autophagy gene ATG4D are associated with a pediatric neurological disorder characterized by hypotonia, joint laxity, and delayed speech and motor development (M. Morimoto)

1156 – Statistical framework uncovers deep intronic splice gain variants implicated in undiagnosed cases (S. Kobren)

1187 – Large scale Cas9 mediated depletion of highly abundant transcripts to expand the interpretable genome and improve the diagnostic yield of clinical RNA Seq (A. Y. Huang)

POSTER PRESENTATIONS

2186 – Bi-allelic variants in neuronal cell adhesion molecule (NRCAM) lead to a novel neurodevelopmental disorder characterized by developmental delay, hypotonia, peripheral neuropathy or spasticity (H. Baris Feldman)

2550 – De novo variants in TCF4 with a suspected gain-of-function mechanism are responsible for a new malformative disease without intellectual disability (E. Colin)

2630 – Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome (M. A. Cousin)

2891 – Prioritizing Research Variants in the NIH Undiagnosed Diseases Program (D. R. Adams)

3002 – Characterizing repeat expansion variation in the Undiagnosed Disease Network cohort (S. Fazal)

3037 – Impaired SNAPC4 function leads to global reduction of canonical splicing events and is associated with a disorder characterized by progressive spasticity, developmental delay, and speech dysarthria (F. G. Frost)

3104 – X-linked recessive mutations in PDZD4 are likely associated with neurodevelopment delay and autism spectrum disorder (M. Sandler)

3410 – De novo damaging variants in the microRNA processor DROSHA are associated with a severe progressive neurological disorder (S. Barish)

3411 – De novo variant in MRTF-B is associated with intellectual disability, minor dysmorphic features, expressive language delay, impulse control issues, and fine motor delay (J. C. Andrews)

3417 – Biallelic NAV2 truncating variants cause a neurodevelopmental disorder with cerebellar cortical dysplasia (J. A. Rosenfeld)

3426 – Loss of function variants in PUS7 dysregulate protein synthesis and are associated with neurodevelopmental delay, microcephaly, and hyperuricemia (K. Garcia)

3428 – Novel PRUNE1 c.933G>A (p.Thr311=) synonymous splice variant induces exon 7 skipping and leads to an atypical presentation of NMIHBA syndrome: Case report and review of the literature (C. Magyar)

3435 – A heterozygous gain-of-function variant in KIF5B causes osteogenesis imperfecta by disrupting the Golgi-primary cilia axis (M. Washington)

3456 – Precision medicine models for undiagnosed and rare disease (L. C. Burrage)

3482 – Personalized structural biology reveals the molecular mechanisms underlying heterogeneous epileptic phenotypes caused by de novo KCNC2 variants (S. Mukherjee)

3502 – Knowledge based artificial intelligence for variant pathogenicity prediction for Mendelian disorders (D. Mao)

The Undiagnosed Diseases Network at the ASHG 2020 Virtual Meeting

The Undiagnosed Diseases Network (UDN) is participating in the American Society of Human Genetics (ASHG) Virtual Meeting from October 27-30, 2020. Click here for a printable list of UDN talks and posters.

PLATFORM PRESENTATIONS

1032 – Transcriptome-directed genomic analysis accelerates diagnosis and overcomes limitations of exome sequencing and chromosomal microarray (D.R. Murdock)

1052 – Somatic Mutations in a Single Residue of UBA1 are Associated with a Severe Adult-Onset Autoinflammatory Disease (D. Beck)

1118 – Identifying rare variant combinations associated with digenic disease in Undiagnosed Diseases Network patients using machine learning (S. Mukherjee)

1300 – Personalized regulatory genomics: Identifying gene dysregulation to solve undiagnosed rare disease cases (E. McArthur)

POSTER TALK

1088 – Bi-allelic loss-of-function variants in Replication Factor C 4 (RFC4) are associated with a neurological disorder characterized by ataxia and incoordination (M. Morimoto)

ON-DEMAND POSTERS

Molecular and Cytogenetic Diagnostics

3306 – Clinical whole genome sequencing increases molecular diagnostic yields of Mendelian disorders in patients with prior negative exome evaluations (P. Liu)

3325 – Establishing molecular diagnoses for rare monogenic disease: Why do we fail? (J. Krier)

3357 – Neurodevelopmental disorders with myoclonic epilepsy in the NIH Undiagnosed Diseases Program (S. Shimada)

Mendelian Phenotypes

3089 – 8 year-old girl with hypokalemic periodic paralysis and SOFT syndrome: Novel, disease-associated variants identified in SCN4A and POC1A (L. Fernandez)

3137 – Clinical sites of the Undiagnosed Diseases Network provide unique contributions to genomic medicine and science. (V. Shashi)

3157 – Dysregulation of protein synthesis due to loss of function of PUS7 is associated with postnatal microcephaly, aggressive self-injurious behavior, speech delay, and global developmental delay (S. Han)

3191 – HIP1R may be associated with a recessive, progressive, neurologic disorder (J. A. Rosenfeld)

3201 – Infantile-onset obesity, tall stature, and macrocephaly: diagnosing atypical presentations of STX16 microdeletion-associated pseudohypoparathyroidism type 1B by genome sequencing in two sisters. (A. Xu)

3206 – Long read genome sequencing identifies a novel inherited multi-exon duplication of EHMT1 in a patient with likely Kleefstra syndrome: A case of parental mosaicism? (C. Reuter)

3234 – Predicted loss-of-function variants in SNAPC4 are associated with a pediatric neurological disorder characterized by progressive neuromuscular spasticity, developmental delay, and speech dysarthria (F. G. Frost)

Molecular Phenotyping and Omics Technologies

3491 – Assessing the utility of RNA sequencing in the diagnosis of rare Mendelian diseases. (D. E. Bonner)

Bioinformatics and Computational Approaches

2027 – Algorithm with O(N) Time Complexity for Detecting Mosaicism in DNA Samples with SNP Chip and Exome Sequencing (A. Rodriguez)

2148 – Leveraging whole genome sequencing (WGS) data in search of known and novel repeat expansion diseases in the Undiagnosed Diseases Program (UDP) (P. Houston)

2168 – NIH Undiagnosed Diseases Program data sharing, part II. Tracking case matches (D. Adams)

2179 – Platform Independent Distributed Model for the Visualization of Exome and Genome Analysis Results (B. N. Pusey)

The Undiagnosed Diseases Network at ASHG 2019

The Undiagnosed Diseases Network will be at the American Society of Human Genetics (ASHG) Annual Meeting in Houston, TX from October 15-19, 2019. Information about the UDN will be available at the National Human Genome Research Institute booth (#227) during exhibit hours.

Click here to view a printable list of UDN presentations. The UDN Coordinating Center team will be sharing live updates from the meeting on Twitter – be sure to follow the conversation using the hashtag #ASHG19!

The Undiagnosed Diseases Network at ACMG 2019

The Undiagnosed Diseases Network will be at the American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting from April 2-6, 2019. Information about the UDN will be available at booth #201 during exhibit hours.

Click here to view a printable list of UDN presentations. The UDN Coordinating Center team will be sharing live updates from the meeting on Twitter– follow along using the hashtag #ACMGMtg19!

The Undiagnosed Diseases Network at ASHG 2018

The Undiagnosed Diseases Network will be at the American Society of Human Genetics (ASHG) Annual Meeting in San Diego, CA from October 16-20, 2018. Information about the UDN will be available at the National Human Genome Research Institute booth (#329) during exhibit hours.

Click here to view a printable list of UDN presentations. The UDN Coordinating Center team will be sharing live updates from the meeting on Twitter – be sure to follow the conversation using the hashtag #ASHG19!

The Undiagnosed Diseases Network at ACMG 2018

The Undiagnosed Diseases Network will be at the American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting from April 10-14, 2018. Information about the UDN will be available at booth #720 during exhibit hours.

Click here to view a printable list of UDN presentations. The UDN Coordinating Center team will be sharing live updates from the meeting on Twitter and Instagram– be sure to follow the conversation using the hashtag #ACMGMtg18!

The Undiagnosed Diseases Network at ASHG 2017

The Undiagnosed Diseases Network will be at the American Society of Human Genetics (ASHG) Annual Meeting in Orlando, Florida from October 17-21, 2017. Information about the UDN will be available at the NIH Common Fund booth (#952) and the NHGRI booth (#855) during exhibit hours.

Click here to view a printable list of UDN presentations. The UDN Coordinating Center team will be sharing live updates from the meeting on Twitter – be sure to follow the conversation using the hashtag #ASHG17!